Heme oxigenase (HEOX) é uma enzima que converte o anel heme em biliverdina, monóxido de carbono (CO) e Fe3+. O CO ativa a guanilil ciclase, com resultante produção de 3?,5?-monofosfato de guanosina cíclico(cGMP) provocando relaxamento da musculatura lisa vascular. Nós verificamos o efeito da inibição aguda da heme oxigenase com zinco protoporfirina (ZnPP IX) sobre a pressão arterial de ratos Wistar machos recebendo dieta hipossódica (0,15% de NaCl), normossódica (1,3% de NaCl) ou hipersódica (8% de NaCl) desde o desmame, com 21 dias de vida. Para isto a pressão arterial caudal (grupo A - 3 e B - 6 meses de idade) e carotídea (grupo C) foram medidas antes e após a administração do inibidor da HEOX ou de veículo (Na2CO3). Em resposta ao ZnPP IX, os animais do grupo A submetidos à sobrecarga salina apresentaram uma significativa diminuição dos níveis pressóricos enquanto que os animais que recebiam dieta hipo e normossódica, apresentaram aumento dos níveis pressóricos. No grupo B e C, após inibição da enzima, não houve modificação dos níveis pressóricos dos ratos em nenhuma das três dietas. Observamos nos três grupos (A, B e C) uma correlação negativa entre a pressão arterial basal (antes da administração de ZnPP) e a área debaixo da curva da variação percentual das pressões arteriais após inibição de HEOX (grupo A: r = 0,66 - P < 0,0001?; grupo B: r = 0,59 - P = 0,006;?; grupo C: r = 0,59 - P < 0,0005?). Nos animais que receberam veículo, esta correlação não ocorreu, exceto para PAS no grupo C. Podemos concluir que a resposta pressórica à inibição da HEOX é modulada pela pressão arterial basal. / The heme ring is hydrolyzed by an enzyme called heme oxygenase (HEOX). The products of that reaction are biliverdin, carbon monoxide (CO) and Fe3+. CO produces vascular smooth muscle cell relaxation due to activation of guanylyl ciclase with the resultant production of 3?,5?-ciclic guanosine monophosphate (cGMP). In the present study the effect on blood pressure due to acute inhibition of HEOX by zinc protoporphyrin IX (ZnPP IX) was observed. Male Wistar rats were fed low (LSD ? 0.15% NaCl), normal (NSD ? 1.3%) or high salt diet (HSD - 8% NaCl) from weaning (21 days-old animals). Tail-cuff blood pressure was measured in group A and B and continuous intra-arterial pressure was evaluated in group C before and after ZnPP IX or vehicle (Na2CO3) administration. In group A, blood pressure decreased in rats on HSD, and increased in the animals on NSD and LSD after ZnPP IX administration. A similar response to ZnPP IX was observed in group B. In group C no change in blood pressure was observed in the rats on the three diets. A negative correlation was obtained between blood pressure measured before ZnPP IX and the area under the curve of the percentual blood pressure change induced by ZnPP IX [(group A: r=0.66 - P<0.0001), (group B: r=0.59 - P=0.006), and (group C: r=0.59 - P<0.0005)]. In the animals that received vehicle, this correlation was not observed. In conclusion, in Wistar rats, the effect of HEOX inhibition by ZnPP IX is modulated by the basal blood pressure levels.

Background and Purpose: Primary nocturnal enuresis (PNE) is a heterogeneous disorder with various underlying pathophysiological mechanisms. Results of our recent studies focused on the relationship of bladder function, sleep and brain function demonstrated a simultaneous occurrence of bladder and brain dysfunction in children with severe refractory PNE. We therefore proposed to use an animal model with altered bladder function to evaluate if abnormalities in bladder function induce functional derangement in brainstem micturition centers and/or sleep-arousal centers. / Materials and methods: In general, the study was divided in to 6 parts. Male Wistar rats (~ 1.5 months) were used for the study. / Study I: Establishment of animal model —— Male Wistar rats (200-220 g) underwent either Sham surgery or surgical reduction of bladder volume (RBV). Animals were used for further Cystometry, EEG, MRS and Cognitive function studies 4-5 weeks postoperatively. / Study II: Conventional Fill Cystometry (CFC) to evaluate bladder functional changes in response to surgical bladder volume reduction —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. CFC was performed under conscious condition for evaluating the functional changes in response to surgical bladder capacity reduction. / Study III: Radiotelemetered EEG study to assess the impact of bladder dysfunction on sleep architecture and cortical arousals in rats —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. Radiotelemeters were implanted in both groups 4 weeks post-operatively. The EEG biopotential and bladder pressure were monitored for 48 hours. Sleep architecture and cortical arousals were then evaluated manually. / Study IV: Evaluation of cognitive function following surgical bladder volume reduction —— Ninety eight rats (RBV=50, SHAM =48) were used for the study. / Morris Water Maze task: A circular plastic translucent pool half-filled with 26 ± 2ºC water, was used in the Morris Animals were given 9 consecutive training (2/day) sessions of Morris Water Maze (MWM) at 4 weeks postoperatively. / 8-arm Radial Maze: Food pellets were randomly placed inside each arm of the maze and the rats were allowed to explore the maze freely for 5 minutes. The rat was allowed to explore the maze for 5 minutes. Total time spent in each arm, total distance traveled in the maze was recorded. / Study V: Magnetic Resonance Spectroscopy to detect functional changes in brain in response to bladder dysfunction elicited by surgical bladder volume reduction —— Proton magnetic resonance spectroscopy was employed to examine brain metabolic changes in 24 rats (RBV=12, SHAM=12). Single voxel 1 H MRS experiments were performed using a 7 T MRI scanner. MR spectra were then processed using the jMRUI software. / Phase VI: Enzyme -linked immunosorbent assay for the assessment of associated changes in neurotransmitters —— Animals were euthanized after MRS study and brain samples were collected. Serotonin and dopamine levels were assessed in 10 mg of tissue extracts from brainstem and cortex, with ELISA kits. / Results: Study I: Bladder reduction surgery did not affect the increase in body weight post -operatively. Average body weight of the RBV and the sham groups were 340.2 ± 47.2 g and 340.5 ± 67.9 g respectively at 4 weeks post operatively. / Study II: Compared to sham group, the maximum cystometric capacity in animals with RBV was remarkably reduced at week 4 (0.78 ± 0.12 ml vs. 1.46 ± 0.22 ml, RBV vs. Sham respectively; p<0.005). Moreover, maximum detrusor pressure during voiding was significantly increased in RBV group at week 4 post operatively (32.4± 2.14 vs.23.27±1.2 5 cm H2O, RBV vs. Sham respectively). / Study III: Light non-repaid eye movement sleep occurred significantly more in RBV rats compared to sham group (61.8% vs 35%). Deep sleep and rapid eye movement sleep occurred significantly less in RBV group compared to that of sham group (30.7% vs 53.4%). / Study IV: Results showed that the RBV group used a significantly longer latency to locate the platform compared to Sham group (24.4s vs 17.19s, RBV vs. Sham respectively, p<0.001).. Moreover, significantly more animals from the RBV group could not complete the visit of the 8 arms of radial maze than that of the sham group. / Study V: Seven metabolites were detected and quantified. The results demonstrated significant changes in the lactate (Lac) metabolism in some specific regions of rat brain. At 4 weeks post - operatively, level of lactate significantly decreased in the hippocampus (43%, P<0.001) cingulate and retrosplenial cortex (29%, p<0.05) of RBV rats compared to that of sham rats. / Study VI: Results demonstrated a significant increase in Serotonin level in the brainstem of RBV rats compared to that of SHAM rats (23.726 + 0.88 ng/ml vs. 1.88 + 0.302 ng/ml). Dopamine levels decreased significantly in brainstem samples of RBV group compared to sham group (2.85 + 0.10 ng/ml vs. 6.85 + 0.84 ng/ml). / Conclusion: Surgical bladder volume reduction of bladder capacity can induce functional changes in the central nervous system. An alteration of the sleep architecture occurred in response to surgical reduction of bladder volume in rats, suggesting that there exists a potential for central consequences of bladder dysfunction. Bladder disorder chronically altered brain energy metabolism. Furthermore, bladder disorder altered the central neurotransmission in the brainstem and cortex. The finding of bladder dysfunction induced significant impairments in cognitive function in RBV rats, suggesting that the alteration in brain energy metabolism may contribute to the behavioral and attention problems, impaired learning and cognitive performance. / 研究背景： 原發性夜間遺尿症（PNE）是一種異質性疾病，涉及多種潛在的病理生理機制。我們最近的研究主要集中在膀胱功能，睡眠和腦功能的關係，結果顯示膀胱和腦功能障礙同時出現在患有嚴重難治性的PNE的兒童。因此，我們建議採用一種已改變膀胱功能的動物模型來評估膀胱功能異常會否引起腦幹排尿中心和/或睡眠 - 覺醒中心的功能紊亂 / 研究工具和方法： 研究被分成6個部分。雄性Wistar大鼠（約1.5個月）被用於研究。 / 研究I： 動物模型的建立 —— 雄性Wistar大鼠（200-220克），會先接受假手術或手術降低膀胱容量（RBV）。手術後4至5週，動物會進行進一步的膀胱測壓，腦電圖，MRS和認知功能研究。 / 研究II： 以常規填充膀胱測壓（CFC）評估減少膀胱容量手術對膀胱功能的變化 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。 CFC是用以評估在有意識的條件下，膀胱因膀胱容量減少的手術而引起的功能變化。 / 研究III： Radiotelemetered腦電圖研究，以評估在大鼠膀胱功能失調對睡眠結構和皮質覺醒的影響 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。膀胱容量減少的手術4週後，Radiotelemeters被植入在兩個組別的大鼠，並監測其腦電生物電勢和膀胱內壓48小時，然後手動評估睡眠結構和皮層覺醒。。 / 研究IV： 評估在膀胱容量減少的手術後對認知功能的影響 —— 103個大鼠（RBV=56，對照= =47）被用於研究。 / Morris水迷宮任務： 一個圓形的塑料半透明池盛載半滿的水，溫度介乎26 - ±2℃，手術4週後，該池被用在莫里斯動物進行連續9次Morris水迷宮（MWM）培訓（每天2次）。 / 八臂迷宮： 食物顆粒被隨機放置在迷宮的每個臂內，大鼠可以自由地探索迷宮5分鐘。大鼠被允許探索迷宮5分鐘。在每個手臂所用的總時間，以及在迷宮行走的總距離都會被記錄。 / 研究V： 以磁共振波譜檢測膀胱容量減少的手術所引起的膀胱功能障礙對腦功能的改變 —— 以質子磁共振波譜研究24隻大鼠腦內的代謝變化(RBV=12，對照==12）。以7 T MRI掃描儀進行磁共振波譜實驗，然後使用jMRUI軟件處理MR譜。 / 第六期： 以酶聯免疫吸附測定法評估神經遞質的相關變化 —— 動物在進行MRS研究後實施安樂死，並收集其腦樣品。從腦幹和皮層提取10毫克組織提取物，使用ELISA試劑盒，以評估羥色胺和多巴胺水平。 / 結果： 研究I： 膀胱容量減少手術並沒有影響體重增加。手術4週後，利巴韋林和對照實驗組的平均體重分別為340.2±47.2克和340.5±67.9克。 / 研究II： 相比起對照實驗組的動物，RBV組的最大膀胱容量顯著降低（0. 0.78 ± 0.12毫升對1.46±0.22毫升），排尿頻率顯著增加（2.53±0.30 對.0.53±0.05/hr）。此外，排尿時最大逼尿肌壓力亦顯著升高（32.0.8±2.19 比.20.37±1.2 5厘米水分子） / 研究III： 相比起對照實驗組的動物，光非快速動眼期睡眠顯著地較多發生於RBV大鼠身上（61.8％對35.6％），深層睡眠和快速動眼期睡眠顯著地較少發生在RBV組（32.3％對52.8％） / 研究IV： 結果表明，RBV組使用了顯著較長的時間來定位平台（24.4s vs. vs.17.19s）。而且，在RBV組，顯著地較多動物無法完成行走8臂的放射狀迷宮。 / 研究V： 進行檢測和定量七種代謝物。結果顯示乳酸（LAC）代謝在大鼠大腦的某些特定區域出現顯著變化。在手術4週後，相比起對照實驗組的動物，RBV組大鼠在海馬體（43％，P <0.001），扣帶和夾肌皮質（29％，P <0.05）的乳酸水平均顯著減少。 / 研究VI： 結果顯示RBV大鼠腦幹的血清素水平較對照實驗組的顯著增加（23.726+0.88納克/毫升與1.88±0.302ng/ml）。RBV大鼠腦幹的多巴胺水平則較對照實驗組的顯著下降（2.850.10納克/毫升與6.85+0.84毫微克/毫升）。 / 結論： 外科膀胱容量減少可誘導中樞神經系統的功能變化。以外科手術減少膀胱容量的大鼠亦引起睡眠結構改變，這顯示膀胱功能障礙對中樞有潛在影響。膀胱疾病長期改變大腦的能量代謝。此外，膀胱疾病亦改變了在腦幹和大腦皮層的中樞神經遞質傳遞。研究發現膀胱功能障礙顯著地損害RBV大鼠的認知功能，顯示改變大腦的能量代謝亦可導致行為和專注力的問題，從而損害學習和認知能力。 / Yeung, Chung Kwong. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 199-230). / Abstracts also in Chinese. / Title from PDF title page (viewed on 14, September, 2016). / Yeung, Chung Kwong. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

O tratamento para síndrome dos ovários policísticos (SOP) inclui como primeira linha de cuidados a mudança de estilo de vida com dieta balanceada e exercícios físicos. Dentre as intervenções nutricionais o jejum intermitente (JI) é uma estratégia alternativa. O objetivo deste estudo foi avaliar o impacto do JI em aspectos metabólicos e reprodutivos em modelo animal de SOP. A SOP experimental foi induzida por injeção subcutânea de propionato de testosterona, em período neonatal. Os animais do grupo Controle receberam injeção subcutânea de óleo de girassol. Após 90 dias de idade, instituiu-se a intervenção: grupo JI recebeu ração padrão em dias alternados enquanto o grupo controle manteve a dieta no esquema habitual. Os grupos experimentais foram: Controle ad libitum (n=10), Controle JI (n=10), SOP ad libitum (n=11) e SOP JI (n=15). Foram realizados: teste de tolerância à insulina (ITT) e à glicose (GTT), esfregaço vaginal, passagem por gaiolas metabólicas e PET/CT para avaliar atividade metabólica de tecido gorduroso. Após 4 semanas de JI, os animais foram eutanasiados e coletados tecido adiposo em região inguinal, perigonadal e mesentérica, adrenal, coração, ovários e útero. Como resultados, identificamos que a ingestão alimentar no grupo SOP foi maior em relação ao Controle, antes e depois da intervenção, assim como a sua massa corporal. Nas gaiolas metabólicas pré-jejum, a ingestão alimentar e hídrica, excreção fecal e urinária foram maiores nos animais SOP. No ITT, a glicemia basal dos animais SOP ADL apresentou-se maior que os Controle ADL. No GTT, a glicemia de jejum das ratas Controle JI era maior que as ratas Controle ADL. O peso da inguinal do grupo SOP JI era menor que SOP ADL. A gordura mesentérica se apresentou menor nos animais Controle JI em relação ao Controle ADL. Controle e SOP JI possuíam menores quantidades de perigonadal quando comparadas as ADL. O peso do coração dos animais SOP ADL era maior que os SOP JI. Grupos SOP apresentaram maior adrenal que os Controle. SOP JI possuía menor peso de ovário em relação aos grupos Controle ADL e JI. Em conclusão, o jejum intermitente reduziu os depósitos de gordura perigonadal e mesentérica dos animais Controle, e inguinal e perigonadal dos animais SOP. Além disso, o JI aumentou a glicemia basal das ratas Controle / Treatment for polycystic ovary syndrome (PCOS) includes as first line of care lifestyle change with balanced diet and exercise. Among the nutritional interventions, intermittent fasting (IF) is an alternative strategy. The objective of this study was to evaluate the impact of IF on metabolic and reproductive aspects in animal models of PCOS. Experimental PCOS was induced by subcutaneous injection of testosterone propionate in the neonatal period. Control animals received subcutaneous injection of sunflower oil. After 90 days of age, the intervention was instituted: IF group received standard ration on alternate days while the control group maintained the diet in the usual scheme. The experimental groups were: Control ad libitum (n = 10), Control IF (n = 10), PCOS ad libitum (n = 11) and PCOS IF (n = 15).The following tests were performed: insulin tolerance test (ITT) and glucose (GTT), vaginal smear, passage through metabolic cages and PET / CT to evaluate the metabolic activity of fatty tissue. After 4 weeks of IF, the animals were euthanized and collected adipose tissue in inguinal region, perigonadal and mesenteric, adrenal, heart, ovaries and uterus. As results, we identified that the food intake in the PCOS group was higher in relation to the Control, before and after the intervention, as well as their body mass. In the pre-fast metabolic cages, food and water intake, fecal and urinary excretion were higher in PCOS animals. In ITT, the basal glycemia of the PCOS ADL animals was higher than the Control ADL. In GTT, the fasting glycemia of Control IF rats was greater than the Control ADL rats. The inguinal weight of the PCOS IF group was less than PCOS ADL. Mesenteric fat was lower in Control IF animals than in Control ADL. Control and PCOS IF had smaller amounts of perigonadal when compared to ADL. The heart weight of the PCOS ADL animals was higher than the PCOS IFs. PCOS groups presented greater adrenal than Control. PCOS IF had lower ovary weight in relation to the ADL and IF Control groups. In conclusion, intermittent fasting reduced deposits of perigonadal and mesenteric fat in Control animals, and inguinal and perigonadal in PCOS animals. In addition, IF increased basal glycemia of control rats

Lee Kai Woo. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 90-104). / Abstracts in English and Chinese. / Acknowledgements --- p.ii / Thesis Committee --- p.iii / Abstracts --- p.v / 論文槪要 --- p.vii / List of figures --- p.viii / List of abbreviations --- p.ix / Chapter Chapter one --- Introduction --- p.1 / Chapter 1.1 --- Drug metabolism and UGTs --- p.1 / Chapter 1.2 --- Natural substrates of UGTs --- p.4 / Chapter 1.3 --- Functions of UGT isoforms: roles of UGT polymorphisms --- p.6 / Chapter 1.4 --- Evolution of the UGT1 gene locus in vertebrates --- p.8 / Chapter 1.5 --- Multiple Variable First Exons: A Mechanism for Cell- and Tissue-Specific Gene regulation --- p.13 / Chapter 1.6 --- Evolutionary Origin of the Variable and Constant Genomic Organization --- p.14 / Chapter 1.7 --- Variable and Constant Genomic Organizations Exist in Mammalian UGTs --- p.20 / Chapter 1.8 --- The history of recombinant UGT expression --- p.20 / Chapter 1.9 --- UGT1A8 --- p.21 / Chapter 1.10 --- Licorice and its active component --- p.24 / Chapter 1.11 --- Enzyme induction in the liver --- p.25 / Chapter 1 12 --- Objectives --- p.28 / Chapter Chapter two --- Methods and Materials --- p.29 / Chapter 2.1 --- UGT1A8 induction studies --- p.30 / Chapter 2.1.1 --- Drug preparation --- p.30 / Chapter 2.1.2 --- Cell viability study with Neutral Red Assay Rat treatment --- p.30 / Chapter 2.1.3 --- Cell treatment --- p.31 / Chapter 2.1.4 --- Rat treatment --- p.31 / Chapter 2.1.5 --- RNA extraction from rat liver and cell culture --- p.31 / Chapter 2.1.6 --- Quantization of RNA --- p.32 / Chapter 2.1.7 --- Denaturing gel electrophoresis for RNA --- p.33 / Chapter 2.1.8 --- Northern hybridization --- p.33 / Chapter 2.1.9 --- Probe for Northern Blotting --- p.34 / Chapter 2.1.10 --- Agarose Gel analysis and Northern Blot analysis --- p.34 / Chapter 2.2 --- Recombinant expression of UGT1A8 in E.coli JM109 --- p.35 / Chapter 2.2.1 --- cDNA synthesis --- p.35 / Chapter 2.2.2 --- Polymerase chain reaction --- p.35 / Chapter 2.2.3 --- Agarose gel electrophoresis for DNA --- p.35 / Chapter 2.2.4 --- "Amplification of target gene, UGT1A8" --- p.36 / Chapter 2.2.5 --- Restriction enzyme digestion of plasmid and insert --- p.36 / Chapter 2.2.6 --- Ligation of plasmid and insert DNA --- p.37 / Chapter 2.2.7 --- Amplification of target plasmid --- p.37 / Chapter 2.2.8 --- Screening of target plasmid --- p.37 / Chapter 2.2.9 --- DNA sequencing --- p.38 / Chapter 2.2.10 --- Transformation of protein expression host --- p.38 / Chapter 2.2.11 --- Confirmation of transformation of protein expression host --- p.38 / Chapter 2.2.12 --- Protein expression --- p.39 / Chapter 2.2.13 --- Protein purification --- p.39 / Chapter 2.2.14 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis --- p.40 / Chapter 2.2.15 --- Confirmation of the protein --- p.40 / Chapter 2.3 --- Characterization of recombinant UGT1A8 --- p.41 / Chapter 2.3.1 --- UGT assay --- p.41 / Chapter 2.4 --- Routine experiment methods --- p.41 / Chapter 2.4.1 --- Determination of protein --- p.41 / Chapter 2.4.2 --- Nucleic acid purification --- p.42 / Chapter 2.4.3 --- Preparation of chemically competent bacterial cells --- p.42 / Chapter 2.4.4 --- Colony PCR --- p.43 / Chapter 2.4.5 --- Plasmid rescue by alkaline lysis --- p.44 / Chapter 2.4.6 --- Charging of His-tagged column --- p.44 / Chapter 2.4.7 --- Washing of His-tagged column --- p.45 / Chapter Chapter three --- Results --- p.46 / Chapter 3.1 --- UGT1A8 Expression in clone9 and H4IIE after treatment with licorice and 18 β glycyrrhentinic acid --- p.46 / Chapter 3.2 --- UGT1A8 induction in wistar and j/j rats after treatment --- p.63 / Chapter 3.3 --- Construction of pRset-UGT 1A8 Vector --- p.70 / Chapter 3.4 --- Purification of recombinant UGT1A8 --- p.75 / Chapter 3.5 --- Screening of substrate of the purified enzyme --- p.77 / Chapter Chapter four --- Discussion --- p.78 / Chapter 4.1 --- Effects of licorice and 18βglycyrrhetinic acid in the induction of UGT1A8 in different cell lines --- p.78 / Chapter 4.2 --- Comparison of wistar and j/j rats in the induction of UGT1A8 --- p.79 / Chapter 4.3 --- Comparison of licorice and 18(3 glycyrrhetinic acid in the induction of UGT1A8 in rats --- p.81 / Chapter 4.4 --- Comparison of in vivo and in vitro of drug treatment --- p.81 / Chapter 4.5 --- Expression of UGT1A7 after drug treatment in vitro --- p.82 / Chapter 4.6 --- Protein expression and purification --- p.83 / Chapter 4.7 --- Substrates of UGT1A8 --- p.83 / Chapter Chapter Five --- Conclusions --- p.86 / References --- p.90 / Appendix --- p.105

A insuficiência cardíaca (IC) é o estágio final de diversas patologias cardíacas e apresenta alta morbimortalidade. Dentre as causas, estão os efeitos cardiotóxicos em pacientes tratados com doxorrubicina (Dox). A fisiopatologia da IC apresenta aumento da atividade barorreflexa e marcada hiperatividade simpática (HS), estado compensatório à redução do débito cardíaco. Porém, a HS prolongada culmina em alterações deletérias para o sistema cardiovascular (SC) com piora do quadro de sintomas. Atualmente muito se discute sobre o papel dos corpúsculos carotídeos (CC) na fisiopatologia da IC devido ao seu reflexo simpatotônico e a melhora de pacientes portadores de IC após a remoção dos CC. O nosso objetivo foi avaliar a influência do CC na evolução da IC induzida pela DOX. Para tal, 35 ratos Wistar machos foram dispostos em 4 grupos: controle Salina (CSAL; n=7) e Controle Dox (CDOX; n=12), Desnervado Salina (DSAL; n=4) e Desnervado Doxo (DDOX; n=12). A desnervação consistiu na ressecção do nervo sinusal bilateral prévia à administração de Dox; a indução da IC ocorreu através de 6 aplicações de Dox, na dose de 2.5mg/kg, pela via IP a cada 4 dias. Após 15 dias do término da indução, os animais foram avaliados pelo ecocardiograma e canulados para registro de pressão arterial invasiva e avaliação hemodinâmica, autonômica, barorreflexa e quimiorreflexa. A análise dos resultados mostra que o grupo CDOX apresentou redução do peso corporal, da sensibilidade baro e quimiorreflexa, hiperatividade simpática acompanhada de redução vagal, redução da morfologia cardíaca associada à disfunção diastólica e sistólica e redução do peso bruto cardíaco e ventricular. A desnervação não foi capaz de reverter os efeitos deletérios causados pela Dox, inclusive a desnervação acentuou a disfunção diastólica e sistólica induzida pela Dox. Concluiu-se que a desnervação carotídea não foi eficiente em melhorar a insuficiência cardíaca induzida pela Dox no modelo experimental proposto / Heart failure (HF) is the final stage of several cardiac pathologies and results in high morbimortality. Among the causes, we can mention the cardiotoxic effects in patients treated with doxorubicin (Dox). The pathophysiology of HF has increased baroreflex activity and marked sympathetic hyperactivity (HS), a compensatory state to the reduction of cardiac output. However, prolonged HS results in worsening of the symptoms. Currently, the role of carotid corpuscles (CC) in the pathophysiology of HF is discussed due improvement of sympathetic reflex presents in patients with HF after CC removal. The objective of this study was to evaluate the influence of CC on the evolution of HF induced by DOX for this method 35 Male Wistar rats arranged in 4 groups: Salina control (CSAL; n = 7) and Dox Control (CDOX; n = 12) Salina Denerved (DSAL; n = 4) and Dox Denerved (DDOX; n = 12). A denervation consisted of bilateral sinus nerve resection prior to Dox administration, induction of HF through 6 Dox applications at a dose of 2.5mg / kg, via IP every 4 days. After 15 days of the end of the induction, the animals were evaluated by echocardiogram and cannulated to record invasive blood pressure and hemodynamic, autonomic, baroreflex and chemorreflex evaluation. Our experiment demonstrated that the CDOX group had reduction of body weight, baro and chemoreflex sensitivity, sympathetic hyperactivity accompanied by vagal reduction, reduction of cardiac morphology associated with diastolic and systolic dysfunction and reduction of gross cardiac and ventricular weight. The denervation is not able to reverse the deleterious effects caused by Dox, including denervation accentuated by Dox-induced diastolic and systolic dysfunction. Based on our results on a carotid denervation it was not effective in improving heart failure induced by Dox

INTRODUÇÃO: A sepse permanece entre as principais causas de morte nos países desenvolvidos e subdesenvolvidos com uma incidência que aumenta a cada ano. O aumento no número de pacientes diabéticos internados em unidades de terapia intensiva (UTIs) também tem chamado a atenção pela complexidade das comorbidades e demais complicações metabólicas encontradas nesta população, contribuindo assim para a desregulação de vias imunológicas e falência de múltiplos órgãos. Diversos estudos sobre distúrbios lipídicos em pacientes diabéticos criticamente enfermos tem sido discutido amplamente na última década com o intuito de identificar características que possam fornecer uma visão mais abrangente das alterações metabólicas e da fisiopatologia desta doença. OBJETIVO: O objetivo deste estudo foi buscar através da análise do perfil lipídico, novos marcadores biológicos e compreender as variáveis da resposta imunoinflamatória encontrada em modelo experimental de sepse, comparando ratos sépticos com e sem diabetes mellitus. MÉTODOS: Utilizamos o modelo de ratos (Wistar) de 8 semanas, divididos em 4 grupos: controle, diabetes (DM), sepse (CLP) e sepse/diabetes (DM+CLP). Através do modelo de punção e ligadura cecal (CLP), induzimos sepse. Através do modelo de Alloxana, induzimos diabetes. Coletamos o plasma para teste de Ensaio Imunoenzimático (ELISA) e células para extração de Ácido Ribonucleico (RNA) que, em seguida, foi submetido a análise através da Reação em Cadeia da Polimerase (PCR). RESULTADOS: A nossa curva de mortalidade demonstrou diferenças significativas entre os grupos analisados (p=0,04). Descobrimos que os grupos CLP vs DM+CLP obtiveram alterações significativas para as expressões de RNAm das lipoproteinas, Fabp4 em adipócitos (p=0,0095) e miócitos (p=0,0152), Acat2 em miócitos (p=0,0303), Gk em leucócitos (p=0,0260) e por ELISA a isoforma Fabp7 (p=0,0152) demonstrou concentrações aumentadas no plasma dos animais diabéticos induzidos a sepse (DM+CLP). CONCLUSÃO: Concluímos que as alterações observadas nas expressões das lipoproteínas revelam um papel importante na patogênese da sepse em animais diabéticos. Acreditamos que através de estudos futuros poderemos complementar a efetividade desde mecanismo complexo e utilizá-lo de forma terapêutica / INTRODUCTION: Sepsis remains among the leading causes of death in developed and underdeveloped countries with an incidence that increases every year. The increased incidence of sepsis in diabetic patients admitted to intensive care units (ICUs) has also drawn attention due to the complexity of the disease and other metabolic complications, leading to immune deregulation, multiple organ failure and high mortality rates. Lipid metabolism in critically ill diabetic patients has been widely investigated in the last decades, since it is an important characteristic in the pathophysiology of this complex disease. OBJECTIVE: The aim of this study was to investigate the lipid profile of diabetic rats, submitted to cecal ligation and puncture. METHODS: Wistar rats 8-week were divided in the following groups: control, diabetes (DM), sepsis (CLP) and sepsis/diabetes (DM+CLP). Plasma was collected for the Enzyme Linked Immuno Sorbent Assay test (ELISA) and the cells were used for Ribonucleic Acid extraction (RNA) that was then analyzed through the Polymerase Chain Reaction (PCR-array). RESULTS: Our mortality curve showed significant differences among the study groups (p=0.04). We found that the CLP vs DM+CLP groups showed significant differences in the mRNA expression of the lipoproteins Fabp4 in adipocytes (p=0.0095) and myocytes (p=0.0152), Acat2 in myocytes (p=0.0303) and Gk in leukocytes (p=0.0260). The protein values of Fabp7 (p=0.0152) exhibited increased plasma concentrations in diabetic animals submitted to sepsis (DM+CLP). CONCLUSION: We conclude that our results of the lipoprotein expression values of several molecules reveal key findings in the pathogenesis of sepsis in diabetic animals and can be used as biomarkers of sepsis in this specific population

O timo secreta substâncias promotoras da sobrevivência de linfócitos e hormônios ligados à dinâmica do citoesqueleto. Esses agentes são produzidos em grande quantidade pelo animal recém-nato, e apresentam efeito homeostático sobre a população de linfócitos T circulantes, por toda a vida. Na sepse, a atrofia dos órgãos linfóides, o surgimento de acúmulos de actina intersticial, e a diminuição dos níveis de fibronectina plasmática guardam relação com a mortalidade. O trabalho aqui descrito procurou detectar o efeito do sobrenadante de cultura de timo de rato Wistar neonato, saudável, sobre a mortalidade e as expressões simultâneas de actina e fibronectina em timos de ratos Wistar adultos submetidos a sepse peritoneal. Foi constatada uma diminuição na expressão de actina e de fibronectina no interstício de timos de ratos Wistar adultos sépticos, tratados com a aplicação intraperitoneal do sobrenadante de explante de timo de ratos neonatos. Tal efeito provocou um aumento da sobrevivência semelhante ao tratamento com meio de cultura apenas ( sem explante), contudo houve uma notável melhora dos sinais clínicos . Não houve qualquer efeito anti-inflamatório, com o tratamento com o sobrenadante, sobre inflamação periférica em animais saudáveis submetidos a injeção intramuscular de glutaraldeído, o que afastou a hipótese de influência sobre a enzima tranglutaminase tecidual, ativada em estados inflamatórios , e responsável pela aglomeração intersticial, da actina originada de células lesadas. O autor concluiu que os efeitos observados pelo tratamento com sobrenadante de cultura de timo de animal recém-nato, podem ser atribuídos a estimulação de mecanismos promotores da integridade celular, frente aos estresses químicos vigentes no meio interno, durante a sepse. O autor sugere que a observação simultânea de actina e fibronectina no timo pode auxiliar nos estudos de tratamentos experimentais da sepse. / The response of septic adult Wistar rats submitted to treatment with supernatant from the culture of thymus of healthy newly-born Wistar rats were observed. Although there has not been significant reduction in mortality compared relation to treatment with culture medium only (without explanted) , it was possible to observe a rapid improvement in the clinical conditions and a lower agglomeration of actin and fibronectin in the thymus of treated animals. We did not observe any anti-inflammatory effect of the supernatant in animals with paw inflammation exclusively, which averted the modulation of the Tissue Transglutaminase Enzyme, agglomerator of the actin released by diseased cells. The author concludes that the treament of sepsis with supernatant stimulated survival in thymus, and suggests that the immuno-hystochemical study of actin and fibronectin in the thymus isa useful method in the analysis of experimental treatments of sepsis.

Recentemente demonstramos o desenvolvimento de fibrose na região subendocárdica (SE) do ventrículo esquerdo (VE) em resposta a sobrecarga de volume na fístula aorto-cava (FAC) crônica. A pressão de perfusão coronariana (PPC) associou-se com fibrose SE e com disfunção do VE subsequentes, sugerindo ser o hipofluxo um dos mecanismos envolvidos no remodelamento ventricular.O remodelamento agudo do VE após FAC ainda é desconhecido. O objetivo deste estudo foi investigar a perfusão e o remodelamento cardíaco nas fases agudas após FAC e as possíveis implicações resultantes sobre a função do VE. Ratos Wistar foram submetidos a cirurgia fictícia (sham) ou a FAC e examinados em 3 períodos de seguimento: 1, 3 e 7 dias. Medidas hemodinâmicas sistêmicas e do VE foram realizadas para calcular a PPC e determinar a função do VE. Cortes teciduais do coração foram submetidos à coloração com HE e Sirius red. A necrose de miócitos, o infiltrado leucocitário e a fração de volume de colágeno foram determinados. O fluxo miocárdico, estimado por microesferas coloridas, a atividade de mieloperoxidase (MPO), a expressão de citocinas e a atividade de metaloproteinase-2 (MMP-2) foram determinados ao final de cada seguimento, todos examinados em duas regiões distintas do VE: SE e não SE. Comparados a sham, os grupos FAC apresentaram (média ± desvio-padrão, P <0,05) menores pressões sistêmicas no dia 1 (PAS: 116±6 vs. 88±17; PAD: 84±13 vs. 51±19 mm Hg/s), no dia 3 (PAS: 121±4 vs. 83±28; PAD: 92±5 vs. 46±21 mm Hg/s) e no dia 7 (PAS: 122±6 vs. 96±21; PAD: 93±6 vs. 66±21 mm Hg/s); maior pressão diastólica final do VE no dia 1 (7±3 vs. 15±6 mm Hg/s), no dia 3 (7±3 vs. 18±3 mm Hg/s) e no dia 7 (7±3 vs. 18±5 mmHg/s); menor PPC no dia 1 (77±14 vs. 37±18 mmHg/s), no dia 3 (86±5 vs. 29±20 mmHg/s) e no dia 7 (86±6 vs. 48±19 mmHg/s). Menor função sistólica e diastólica do VE no dia 1 (+dP/dt: 7898±4045 vs. 5828±2262; -dP/dt:. 6626±1717 vs 4728±863 mmHg/s) e no dia 7 (+dP/dt: 7924±2317 vs. 4564±2044; -dP/dt: 6435±1302 vs. 4750±1442 mmHg/s). Houve maior necrose de miócitos no dia 1 no SE (114±5 vs. 208±8) e no não SE (27±3 vs. 42±10) e no dia 3 no SE (82±12 vs. 148±31) e no não SE (21±3 vs. 31±6); maior infiltrado leucocitário no dia 1 no SE (48±5 vs. 84±13) e no não SE (33±4 vs. 40±6), no dia 3 no SE (48±10 vs. 117±13) e no não SE (41±6 vs. 65±8) e no dia 7 no SE (33±5 vs. 50±6) e no não SE (27±6 vs. 38±7); maior fibroplasia no dia 3 no SE (11± 2,6 vs 26±10) e no dia 7 no SE (11±2,3 vs 47±11); maior fibrose no dia 1 no não SE (1,2±0,2 vs. 1,7±0,5), no dia 3 no SE (1,7±0,3 vs. 5,4±0,1) e no não SE (1,4±0,3 vs. 1,8±0,3) e no dia 7 no SE (1,8±0,4 vs. 10,3±2,3) e no não SE (1,7±0,1 vs. 2,8±0,7). O fluxo miocárdico total no dia 7 foi menor, mais intensamente no SE do que no não SE (6.7±1.2 vs. 2.7±1.6 e 7.5±1.3 vs. 4.8±2.6 mL/min/g). Houve maiores níveis de IL-1 no SE e não SE no dia 1 (1050±145 vs. 4225±792 e 1070±138 vs. 4084±359 pg/mg); de TNF- no SE no dia 3 (1415±447 vs. 2037±200 e 1387±279 vs. 1412±301 pg/mg) e IL-6 no SE no dia 7 (3499±397 vs. 4955±429 e 3653±331 vs. 4297±743 pg/mg). No grupo FAC, os animais com PPC <60 mmHg comparados àqueles com PPC >60 mmHg apresentaram maior atividade de MMP-2 no SE e no não SE no dia 1 (69.1±7 e 66.1±7.0 vs. 13.2±4.0 e 11.2±3.4 %), no SE no dia 3 (104.7±39.5 e 22.3±9.0 vs. 26.3±11.3 e 11.5±2.7 %) e no SE do dia 7 (60.5±12.7 e 48.7±4.2 vs. 29.2±8.0 e 6.7±5.8 %). A PPC apresentou correlação direta e significativa com o fluxo do SE (R=0,65), e com o fluxo do não SE (R= 0,62). O fluxo do SE, porém não o do não SE, apresentou correlação direta e significativa tanto com a +dP/dt (R=0,62) quanto com a dP/dt (R=0,67). A PPC apresentou correlação inversa e significativa com a MMP-2 no dia 1 (R=0,86), no dia 3 (R=0,88) e no dia 7 (R=0,93). O remodelamento cardíaco após FAC aguda caracteriza-se por dano isquêmico no SE, resultante da queda da perfusão e implica em disfunção precoce do VE. / Recently, we have demonstrated that fibrosis develops within the subendocardial region (SE) of the left ventricle (LV) in response to chronic volume overload following aortocaval fistula (ACF). Initially low coronary driving pressure (CDP) was associated with subsequent SE fibrosis and LV dysfunction, suggesting that prior low myocardial perfusion may be one of the mechanisms involved in LV remodeling. This study aimed at investigating the role of myocardial blood flow (MBF) in the development of LV remodeling, particularly within SE, during the acute phases of ACF. Wistar rats were submitted to sham (SH) or ACF operations and examined after 1, 3, and 7 days. Apart from haemodynamics, histology (HE- and Sirius red-stained tissue sections), microsphere MBF, and biochemical studies were undertaken in two different LV myocardial regions: SE and non-SE. Compared with SH, ACF showed (mean±S.D.) lower systemic and higher LV end-diastolic pressures resulting in lower CDP at days 1 (77±14 vs. 37±18 mmHg/s), 3 (86±5 vs. 29±20 mmHg/s), and 7 (86±6 vs. 48±19 mmHg/s) with lower systolic and diastolic LV function at days 1 (+dP/dt: 7898±4045 vs. 5828±2262; -dP/dt:. 6626±1717 vs 4728±863 mmHg/s), and 7 (+dP/dt: 7924±2317 vs. 4564±2044; -dP/dt: 6435±1302 vs. 4750±1442 mmHg/s). There was a higher number of myocyte necrotic cells (cells/mm2) within SE (114±5 vs. 208±8) and non-SE (27±3 vs. 42±10) at day 1, and within SE (82±12 vs. 148±31) and non-SE (21±3 vs. 31±6) at day 3; a higher number of leukocyte cells within SE (48±5 vs. 84±13) and non-SE (33±4 vs. 40±6) at day 1, within SE (48±10 vs. 117±13) and non-SE (41±6 vs. 65±8) at day 3, and within SE (33±5 vs. 50±6) and non-SE (27±6 vs. 38±7) at day 7; a greater fibroplasia within SE (11± 2,6 vs 26±10) at day 3, and within SE (11±2,3 vs 47±11) at day 7; a greater fibrosis deposition within SE (1,7±0,3 vs. 5,4±0,1%) and non-SE (1,4±0,3 vs. 1,8±0,3%) at day 3, and within SE (1,8±0,4 vs. 10,3±2,3%) and non-SE (1,7±0,1 vs. 2,8±0,7%) at day 7. Compared with controls, ACF showed increased IL-1 levels within SE and non-SE at day 1 (1050±145 vs. 4225±792 and 1070±138 vs. 4084±359 pg/mg); increased TNF- levels within SE at day 3 (1415±447 vs. 2037±200 pg/mg); increased IL-6 levels within SE at day 7 (3499±397 vs. 4955±429 pg/mg). Compared with ACF rats with CDP >60 mmHg, MMP-2 activity was increased in rats with CDP 60 mmHg within SE and non-SE at day 1 (13.2±4.0 vs. 69.1±7.6 and 11.2±3.4 vs. 66.1±7.0%), and within SE at day 3 (26.3±11.3 vs. 104.7±39.5 and 11.5±2.7 vs. 22.3±9.0%l). At day 7, MBF was more pronouncedly reduced within SE than within non-SE (6.7±1.2 vs. 2.7±1.6 and 7.5±1.3 vs. 4.8±2.6 mL/min/g). CDP was positively and significantly related to MBF in both SE (R=0.65) and non-SE (R= 0.62). MBF within SE was directly and significantly related to both +dP/dt (R= 0,61) and dP/dt (R=0,67). CDP showed negative and significant correlations with SE MMP-2 at days 1 (R=0.86), 3 (R=0.88), and 7 (R=0.93). LV remodeling during the acute phases of ACF occurs within the SE predominantly, results from low perfusion pressure, and contributes to early LV dysfunction.

O tratamento cirúrgico mais utilizado para a reparação das lesões de nervos periféricos com perda de substância é através de auto-enxertia de nervo. Essa técnica produz alterações na área doadora e muitas vezes não se dispõe de tecido suficiente para grandes perdas de tecido neural. Desta forma é necessária a busca de novas técnicas, menos traumáticas e mais simples, visando eliminar a morbidade na área doadora e prover a quantidade necessária de tecido para a regeneração neural. O objetivo desse trabalho foi comparar, em ratos Wistar, o grau de regeneração neural, utilizando-se de análise histológica e análise funcional, através de interposição de enxerto autógeno de nervo (Grupo A), veia autógena conservada em glicerol (Grupo B) e enxerto alógeno de nervo conservado em glicerol (Grupo C) para correção de defeito de 5 mm de nervo fibular. Quinze ratos machos da raça Wistar, com peso variando entre 200 e 300g, e idade ao redor de oito semanas foram divididos em três grupos de cinco animais de acordo com o tratamento empregado. Para a coleta de segmentos de nervos alógenos, foram escolhidos cinco ratos da Raça Sprague-Dawley, com sexo, idade e peso semelhantes ao da raça Wistar. Os animais foram submetidos à avaliação funcional (\"walking track analysis\") imediata, com três semanas e com seis semanas e sacrificados para realização dos estudos histológicos com a coloração de tetróxido de ósmio. Na análise microscópica das lâminas, realizada, em todos os grupos foram visualizados pequenos fascículos contendo axônios mielinizados de tamanhos variados e degeneração Walleriana em pequeno número de axônios. Nos grupos B (Veia autógena conservada em glicerol) e C(Nervo alógeno conservado em glicerol) o escape de fibras axonais mielinizadas para fora dos limites do epineuro e o processo inflamatório local foram menores que o do grupo A (Auto-enxertia). Em relação à avaliação funcional, onde foi utilizada a análise estatística por meio do modelo de análise de variância com medidas repetidas e o de comparações múltiplas de Bonferroni (p<0.05), não houve diferença estatisticamente significativa entre as recuperações funcionais do nervo fibular independente do tipo de reparação utilizada em nenhum período avaliado. / The most used surgical treatment of peripheral nerves for the repair of injuries with loss of substance is using nerve autograft. This technique produces alterations in the donor area and often not sufficient tissue is available for great losses of neural tissue. Thus the need for new less traumatic and simpler techniques is needed in order to eliminate morbidity in the donor area and to provide the necessary amount of tissue for neural regeneration. The objective of this study was to compare, in Wistar rats, the degree of neural regeneration, using histological and functional analysis through interposition of autogenous nerve graft (Group A), autogenous vein preserved in glycerol (Group B) and allogenous graft preserved in glycerol (Group C) for the correction of a 5-mm defect of fibular nerve. Fifteen male Wistar rats, weighing between 200 and 300 g and approximately 8 weeks old were divided into 3 groups of five animals according to the used treatment. For the collection of autogenous nerve segments 5 Sprague-Dawley rats were chosen, with similar sex and age as the Wistar rats. The animals were submitted to immediate functional evaluation (walking track analysis), at 3 and 6 weeks and sacrificed for histologic studies using osmium tetroxide stain. On microscopic analysis of the slides, performed in all groups, small fascicles containing myelinated axons of varied sizes and wallerian degeneration in a small number of axons were visualized. In Groups B (autogenous vein preserved in glycerol) and C (allogenous nerve preserved in glycerol) escape of axonal myelinated fibers outside the limits of the epineurium and the local inflammatory process were less than in Group A (autograft). Regarding functional evaluation, where statistical analysis by variance analysis using the models of repeated measures and that of Bonferroni\'s multiple comparisons were used (p<0.05) there was no statistically significant difference between functional recoveries of the fibular nerve independent of the type of repair used in any evaluated period.

Heme oxigenase (HEOX) é uma enzima que converte o anel heme em biliverdina, monóxido de carbono (CO) e Fe3+. O CO ativa a guanilil ciclase, com resultante produção de 3?,5?-monofosfato de guanosina cíclico(cGMP) provocando relaxamento da musculatura lisa vascular. Nós verificamos o efeito da inibição aguda da heme oxigenase com zinco protoporfirina (ZnPP IX) sobre a pressão arterial de ratos Wistar machos recebendo dieta hipossódica (0,15% de NaCl), normossódica (1,3% de NaCl) ou hipersódica (8% de NaCl) desde o desmame, com 21 dias de vida. Para isto a pressão arterial caudal (grupo A - 3 e B - 6 meses de idade) e carotídea (grupo C) foram medidas antes e após a administração do inibidor da HEOX ou de veículo (Na2CO3). Em resposta ao ZnPP IX, os animais do grupo A submetidos à sobrecarga salina apresentaram uma significativa diminuição dos níveis pressóricos enquanto que os animais que recebiam dieta hipo e normossódica, apresentaram aumento dos níveis pressóricos. No grupo B e C, após inibição da enzima, não houve modificação dos níveis pressóricos dos ratos em nenhuma das três dietas. Observamos nos três grupos (A, B e C) uma correlação negativa entre a pressão arterial basal (antes da administração de ZnPP) e a área debaixo da curva da variação percentual das pressões arteriais após inibição de HEOX (grupo A: r = 0,66 - P < 0,0001?; grupo B: r = 0,59 - P = 0,006;?; grupo C: r = 0,59 - P < 0,0005?). Nos animais que receberam veículo, esta correlação não ocorreu, exceto para PAS no grupo C. Podemos concluir que a resposta pressórica à inibição da HEOX é modulada pela pressão arterial basal. / The heme ring is hydrolyzed by an enzyme called heme oxygenase (HEOX). The products of that reaction are biliverdin, carbon monoxide (CO) and Fe3+. CO produces vascular smooth muscle cell relaxation due to activation of guanylyl ciclase with the resultant production of 3?,5?-ciclic guanosine monophosphate (cGMP). In the present study the effect on blood pressure due to acute inhibition of HEOX by zinc protoporphyrin IX (ZnPP IX) was observed. Male Wistar rats were fed low (LSD ? 0.15% NaCl), normal (NSD ? 1.3%) or high salt diet (HSD - 8% NaCl) from weaning (21 days-old animals). Tail-cuff blood pressure was measured in group A and B and continuous intra-arterial pressure was evaluated in group C before and after ZnPP IX or vehicle (Na2CO3) administration. In group A, blood pressure decreased in rats on HSD, and increased in the animals on NSD and LSD after ZnPP IX administration. A similar response to ZnPP IX was observed in group B. In group C no change in blood pressure was observed in the rats on the three diets. A negative correlation was obtained between blood pressure measured before ZnPP IX and the area under the curve of the percentual blood pressure change induced by ZnPP IX [(group A: r=0.66 - P<0.0001), (group B: r=0.59 - P=0.006), and (group C: r=0.59 - P<0.0005)]. In the animals that received vehicle, this correlation was not observed. In conclusion, in Wistar rats, the effect of HEOX inhibition by ZnPP IX is modulated by the basal blood pressure levels.