A medicina periodontal vem mostrando uma associação entre a doença periodontal (DP) e doenças sistêmicas. Entretanto, são poucos os estudos que têm focado no impacto da hipertensão arterial sistêmica na progressão da periodontite. A relação entre estas duas patologias envolve o processo de inflamação, uma vez que a hipertensão está associada à disfunção endotelial. O objetivo deste estudo foi avaliar, morfometricamente, se a hipertensão afeta a progressão da DP através do aumento da perda óssea alveolar mesmo após a remoção da ligadura. Utilizando-se um modelo de periodontite induzida por ligadura, 20 ratos hipertensos (Spontaneously Hypertensive Rats - SHR) e 20 ratos normotensos (Wistar Kyoto - WKY) foram distribuídos nos seguintes grupos: WKY-C, WKY-DP, SHR-C e SHR-DP (C grupo controle e DP grupo com doença periodontal). Nos grupos com DP os 1°s molares inferiores receberam ligadura com fio de algodão no início do experimento. Após 10 dias, metade dos animais de cada grupo foi sacrificada e a outra metade teve suas ligaduras removidas. No 21° dia (11 dias após a remoção das ligaduras), os animais restantes foram sacrificados. As mandíbulas tiveram seu tecido mole removido e foram submetidas à análise morfométrica, medindo-se a distância entre a crista óssea alveolar e a junção cemento-esmalte (COA-JCE, mm) em todos os grupos. Aos 10 dias, os grupos com DP mostraram uma perda óssea maior (p<0.05) que seus controles (SHR-DP = 0.72 ± 0.05; SHR-C = 0.39 ± 0.04; WKY-DP = 0.75 ± 0.04 e WKY-C = 0.56 ± 0.04). Após a remoção das ligaduras, a perda óssea acumulada foi superior (p<0.05) àquela aos 10 dias com ligadura, apenas no grupo SHR-DP (0.94 ± 0.13 mm). Foram observados 32% de perda óssea adicional após a remoção das ligaduras no grupo SHR-DP e apenas 17% no grupo WKY-DP. Os ratos SHR (83% e 102%) apresentaram um padrão de perda óssea diferente e mais severa que os WKY (32% e 26%) comparando-se com seus respectivos controles, tanto aos 10 quanto principalmente aos 21 dias. Enquanto que a perda óssea nos WKY tendeu a diminuir após a remoção das ligaduras, os SHR apresentaram uma progressão da perda óssea no 21° dia. Portanto, pode-se especular que a hipertensão está associada com uma perda óssea alveolar mais severa, mesmo após a remoção das ligaduras, e que pode perpetuar a progressão da periodontite. / Periodontal medicine has been showing an association between periodontal disease (PD) and systemic diseases. However, few studies have focused on the impact of hypertension on the progression of periodontitis. The correlation of both conditions involves the inflammatory process, once hypertension is associated to endothelial dysfunction. The purpose of this study was to evaluate morphometrically whether hypertension affects PD progression by enhancing bone loss even after ligature removal. Using a ligature-induced periodontitis model, 20 Spontaneously Hypertensive Rats (SHR) and 20 normotensive rats (Wistar Kyoto - WKY) were assigned to one of the following groups: WKY-C, WKY-PD, SHR-C and SHR-PD (C control group, and PD periodontitis group). On PD groups, the first mandibular molar received a cotton ligature at baseline. After 10 days, 5 animals of each group were sacrificed and the ligatures of the other animals were removed. On the 21th day (11 days without ligatures), the remaining animals were sacrificed. The jaws were defleshed and the distances between the alveolar bone crests and the cementoenamel junctions (ABC-CEJ, mm) were measured in all groups. After 10 days, the PD groups showed more bone loss (p<0.05) than the controls (SHR-PD = 0.72 ± 0.05; SHR-C = 0.39 ± 0.04; WKY-PD = 0.75 ± 0.04 and WKY-C = 0.56 ± 0.04 mm). After ligature removal, the culmulative bone loss was worse (p<0.05) than that one at 10 days with ligature only in SHR-PD group (0.94 ± 0.13 mm). It was observed 32% of additional bone loss in SHR-PD group and only 17% in WKY-PD. The SHR animals (83% and 102%) showed a different and more severe pattern of bone loss than WKY (32% and 26%) related to their respectively controls, at 10 and mainly at 21 days. After ligature removal, bone loss in WKY group tended to diminish, while SHR showed a progressive bone loss in 21° day. Therefore, it may be speculated that the hypertensive condition is associated with an advanced bone loss even after ligature removal that may perpetuate the progression of periodontitis.

Orientador: Carlos Alan Candido Dias Junior / Resumo: INTRODUÇÃO: O tecido adiposo perivascular (PVAT) libera sob condições fisiológicas fatores de relaxamento derivados do tecido adiposo (ADRF), que possivelmente desempenham um papel importante na modulação do tônus vascular. Foi demonstrado que a inativação de canais de potássio sensíveis ao ATP (KATP) aboliu o efeito anticontratil do PVAT. Outros estudos mostraram que o sulfeto de hidrogênio (H2S) é produzido pelo PVAT devido a expressão da sua enzima precursora cistationina gamma liase (CSE) e que o H2S atua através ativação dos KATP. Além disso, o PVAT sofre uma disfunção em condições fisiopatológicas como a hipertensão. No entanto, seus efeitos ainda não são bem explorados durante a hipertensão gestacional. Portanto, nosso objetivo foi examinar o envolvimento do H2S derivado do PVAT na modulação do tônus vascular de ratas prenhes hipertensas e normotensas. MÉTODOS: Foram realizadas curvas concentração-resposta induzidas pela fenilefrina na presença e ausência de PVAT e endotélio em ratas prenhes normotensas (Norm- Preg) e hipertensas (HTN-Preg). A pressão arterial materna, os parâmetros fetais e placentários, a angiogenese e os níveis de H2S também foram avaliados. RESULTADOS: A hipertensão gestacional foi associada ao desequilíbrio angiogênico e a restrição do crescimento fetal e placentário e o PVAT não se mostrou disfuncional. Além disso, sob a formação estimulada de H2S pelo PVAT, mas não no endotélio, houve redução nas curvas concentração-resposta à fenilefrina em aor... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: INTRODUCTION: Perivascular adipose tissue (PVAT) releases diffusible adipocyte- derived relaxing factors (ADRFs) under physiological conditions, which possibly play key roles to modulate the vascular tone. It was demonstrated that the inactivation of ATP-sensitive potassium channels (KATP channels) impaired the anticontractile effect of PVAT. Further studies have shown that hydrogen sulfide (H2s) is released by PVAT due to the expression of cystathionine gamma lyase (CSE) and that (H2s) acts through the activation of KATP channels. In addition, PV A T is impaired in pathophysiological situations such as hypertension. However, it is not yet well explorated during hypertension in pregnancy. Therefore, we aimed to examine the involvement of PVAT-derived H2S to modulate the vascular tone in aorta from normotensive and hypertensive pregnant rats. METHODS: Phenylephrine-induced contractions in the presence and absence of PVAT and endothelium in aortas from normotensive pregnant (Norm-Preg) and HTN-Preg rats were investigated. Maternal blood pressure, fetal-placental parameters, angiogenesis and H2S levels were also assessed. RESULTS: Hypertensive pregnancy associated with angiogenic imbalance and fetal- placental growth restrictions revealed that there is no PVAT dysfunction. Moreover, under stimulated H2S formation PVAT, but not endothelium, reduces phenylephrine-induced contractions in aortas from HTN-Preg rats. Also, H2S synthesis inhibitor abolishes anticontractile effects disp... (Complete abstract click electronic access below) / Mestre

West African immigrants appear to carry a heavier burden of hypertensive heart disease than the native-born African Americans in the United States. In this study, I used the socioecological model theory as a guide to examine the association between perceived stress, length of stay in United States, smoking status, housing conditions, and the risk of hypertensive heart disease among West African immigrants, ages 18 - 54 years in DeKalb County, Georgia. In this quantitative, cross-sectional design, self-reported data were collected from a sample of West African immigrant (N=107) in the DeKalb County of Georgia, using a demographic data/screening sheet and the Perceived Stress Scale. Multivariate logistic regression analysis was used to determine the association between hypertensive heart disease and perceived stress, smoking status, length of stay in the United States, and housing condition, having adjusted for the modifying variables age and education. Results indicated that length of stay in the United States [p =.019, Phi =.331], housing condition [p=.156, R2 =.019], smoking status [p=.050, R2 =.036] and experienced perceived stress experienced [p=.312, R2=.010] are associated with risk of developing hypertensive heart disease. There was a statistically significant association between age [p=.002] and the development of hypertensive heart disease. The result of this study can contribute to positive social change by helping public health agencies to target some of the identified risk factors for hypertensive heart disease in foreign born African American population so as to mitigate the adverse health outcomes associated with hypertensive heart disease.

Angiotensin II signals cardiovascular disease through metalloproteinases including MMP-2, MMP-7 and ADAM-17/TACE. We hypothesized that these metalloproteinases regulate each other at the transcriptional level. Further, MMP-2, being a major gelatinase in cardiac and vascular tissue, could mediate angiotensin II-induced cardiovascular disease. We studied the development of hypertension (by tail cuff plethysmography), cardiac hypertrophy (by M-mode echocardiography and qRT-PCR analysis of hypertrophy marker genes) and fibrosis (by collagen staining and qRT-PCR analysis of fibrosis marker genes) in mice receiving angiotensin II. Angiotensin II induced hypertension, cardiac hypertrophy and fibrosis which correlated with an upregulation of MMP-2. Downregulation of MMP-2 by pharmacological inhibition and RNA interference attenuated hypertension but not cardiac hypertrophy or fibrosis. Downregulation of MMP-7 or ADAM-17/TACE by RNA interference attenuated angiotensin II-induced MMP-2 upregulation as well as hypertension, cardiac hypertrophy and fibrosis. We conclude that MMP-2 selectively mediates angiotensin II-induced hypertension under the transcriptional control of MMP-7 and ADAM-17/TACE.

A functional beverage, designed to be cardio-protective, was formulated, using a blend of juices of cranberry (Vaccinium macrocarpon L), blueberry (Vaccinium angustifolium Aiton.), apple (Malus domestica L.), ginger (Zingiber officinale Roscoe) and selected cardio-protective ingredients. Membrane filtration enhanced the antioxidant properties of the fruit juices. Ultrasound-assisted water extract of ginger showed potential antioxidant activities. The selected fruit juice combination, 50% blueberry; 12.5% cranberry; and 37.5% apple, showed higher consumer acceptability. Incorporation of functional ingredients at 10% RDI and 2% (v/v) ginger extract did not affect the sensory properties of the beverage. Phenolic concentration, FRAP value, and % LDL oxidation inhibition of the formulation were 1024 mg GAE/L, 3114 mg TE/L and 45%, respectively. Diet supplementation with the formulation resulted in lower serum and liver lipid levels in spontaneously hypotensive rats. Blood pressure was reduced by the formulation after two but not four weeks supplementation.

No description available.

Hypertension is a major health problem worldwide. In 1999-2000, 29% or 3.6 million Australians aged 25 yrs and over had high blood pressure (> 140 / 90 mmHg) or were on medication for the condition. It is estimated that about one billion of the world’s population has hypertension and that this will increase to 1.56 billion by 2025. Although antihypertensive drugs have been relatively successful in attenuating elevated blood pressure (BP) and in reducing adverse outcomes, control of BP depends on continuation of therapy. Drugs may have undesirable side effects which diminish compliance and BP may be resistant to treatment. Gene transfer approaches may potentially provide a tool to control BP. RNA interference (RNAi) is a new tool for the study of gene function, producing specific down regulation of protein expression. I tested the hypothesis that angiotensin II type 1 receptor (AT1R) inhibition using RNAi technology would result in sustained reduction of blood pressure in the spontaneously hypertensive rat (SHR). To enable in vivo gene delivery into animal models of hypertension, I have developed small interfering RNA (siRNA) inhibition of AT1R mRNA delivered in a DNA plasmid (pPlasRi-AT1R). Transfection of the recombinant plasmid into a mammanlian cell line resulted in strong expression of the transgenes and a significant reduction in the level of AT1R expression. pPlasRi-AT1R plasmid DNA was intravenously injected into adult spontaneously hypertensive rats at 1.5mg/kg. Telemetric blood pressure transducers were implanted into eight month old male SHR for long-term recording of blood pressure. Twenty-four hour intra-arterial blood pressure was measured weekly. After a 2 week control period animals were injected via the tail vein with AT1R DNA plasmid (n=6), control plasmid containing green fluorescent protein (GFP, n=6) or saline (NaCl, n=6)) and followed for 8 weeks. Additional animals were treated with the DNA plasmid or saline and euthanized at 0, 1, 2, 4, 6 and 8 weeks for determination of tissue AT1R expression using RT-PCR. Aims: (i) To develop an accurate radio-telemetry BP recording method in the SHR, (ii) To design rational siRNA sequences and select of methods for effective silencing in vitro, (iii) To measure the expression of DNA delivered RNAi-AT1R plasmid in vitro and in vivo, and (iv) To determine the in vivo effect of systemic delivery of DNA AT1R plasmid on BP. Methods: Continuous 24 h arterial BP was recorded by radio-telemetry using Maclab hardware and a transducer fixed in the abdominal aorta connected to a transmitter in the abdominal cavity. Data was analyzed using software specifically written for the project. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect AT1R transcripts in various tissues following in vivo AT1R gene delivery. BP was monitored weekly for 8 weeks following 1.5 mg DNA delivered RNAi -AT1R plasmid delivery into 8-month-old SHR by tail vein injection. SHR injected with DNA enhanced green fluorescent protein (eGFP) plasmid or saline served as controls. Results: Weekly 24 h BP was successfully recorded for up to 10 weeks. Following transfection with DNA delivered RNAi -AT1R plasmid in vitro, expression of AT1R in transfected cells was determined by western blot, immunofluorescence and flow cytometry. Furthermore, RT-PCR was employed to confirm the AT1R mRNA levels. Following systemic delivery of RNAi-AT1R plasmid into middle-aged SHR, in animals injected with RNAi plasmid control blood pressure (150 +/- 1mmHg) was reduced 1week after injection (145 +/- 0.5 mm Hg, p<0.05) with maximal reduction 4 weeks after injection (127 +/- 1 mmHg, p<0.01). Blood pressure returned to control level by 8 weeks. There was no change in blood pressure in GFP plasmid or saline injected animals. Tissue expression of AT1R in heart, lung, kidney and liver was reduced following AT1R plasmid injection and was associated with reduction in pressure (r=0.99, p<0.05 for each tissue). There were no significant adverse clinical or biochemical effects. AT1R silencing resulted in significant blood pressure reduction in 8 month old male SHR for approximately 2 months. There was a significant decrease in endogenous AT1R gene expression in tissues as determined by RT-PCR. The results suggest that the systemic delivery of siRNA against AT1R mRNA by DNA-based plasmid vector may have potential for gene therapy of hypertension and that further studies with the plasmid packaged into a recombinant DNA vector for a long-lasting siRNA effect are warranted. RNAi technology with inhibition of AT1R offers a potential new paradigm for the management of high blood pressure. Conclusions: Transfection of cells with DNA delivered RNAi -AT1R plasmid resulted in detection of AT1R transcript in transfected cells confirming a silencing effect in vitro. Significant BP reduction was induced in a group of middle-aged SHR following systemic delivery of DNA plasmid incorporating the siRNA against the AT1R gene. This correlated with significant decrease of endogenous AT1R in various tissues which supported the role of the gene therapy approach in producing a reduction in BP. In summary, the thesis lays the foundation for DNA delivered RNAi mediated AT1R gene delivery as a therapeutic strategy for hypertension. Future work should consider the possible benefits of DNA vector driven AT1R shRNA plasmid containing a regulated tissue-selective promoter and explore approaches which might extend the time during which the hypotensive effect is present

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 2001. / Typescript. Bibliography: leaves 161-195.

A hipertensão arterial sistêmica (HAS) é um problema de saúde pública, geralmente associada a outras doenças, como obesidade, diabetes, doença renal, aterosclerose, acidente vascular cerebral (AVC) e identificado como um dos fatores de risco mais prevalentes para o desenvolvimento de doenças cardiovasculares. Orgãos-alvo, como coração, rins, cérebro e olhos, são comumente afetados em pacientes hipertensos. No entanto, o dano testicular causado pela hipertensão não foi claramente definido. A hipertensão é um fator de risco bem estabelecido para a disfunção erétil, mas sua relação com o dano testicular e a fertilidade masculina não é claramente compreendida. Este estudo avalia a morfologia testicular e alguns parâmetros espermáticos de ratos espontaneamente hipertensos (SHR), virgem de tratamento e tratados com enalapril. Ratos SHR foram distribuídos em dois grupos, um grupo hipertenso (H), e um grupo tratado com enalapril (HE). Ratos Wistar-Kyoto (WKY) foram utilizados como controles. A pressão arterial sistólica foi medida semanalmente, até o final do experimento. A concentração de espermatozóides, motilidade e viabilidade foram determinadas em amostras coletadas da cauda do epidídimo. Métodos estereológicos foram usados para analisar objetivamente a morfologia testicular macroscopicamente e microscopicamente. Todos os dados foram analisados por ANOVA com pós-teste de Tukey, considerando p <0,05. Ao final do experimento a pressão arterial sistólica no grupo HE (153,9 mmHg 21,03 ) foi semelhante a dos animais pertencentes ao grupo WKY (153,4 24,41) e menor que a dos animais H (205,1 24,9). A concentração espermática do grupo H (1,31 x 107 sptz/ml 0,27) foi inferior à do grupo WKY (2,11 x 107 sptz/ml 0,34), entretanto o controle da pressão arterial com o enalapril melhorou este parâmetro e a concentração espermática do grupo HE (2,46 x 107 sptz/ml 0,54) foi semelhante a do WKY. A densidade volumétrica vascular também foi alterada no grupo de hipertensos, enquanto que os animais do grupo HE foram semelhantes aos controles. O epitélio seminífero dos animais HE apresentou a maior densidade volumétrica, indicando um possível efeito protetor indireto do enalapril na espermatogênese. Neste modelo animal, a HAS promoveu alterações morfológicas no testículo, com conseqüências sobre a produção de espermatozóides. O controle da pressão arterial com o enalapril protegeu o testículo destas alterações, restabelecendo a produção normal dos espermatozóides. / Hypertension is a major public health problem, usually associated with other disorders such as obesity, diabetes, kidney disease, atherosclerosis, stroke and identified as one of the most prevalent risk factors for developing cardiovascular diseases. Target organs, such as heart, kidney, brain and eyes, are very commonly affected in hypertensive patients. However the testicular damage caused by hypertension has not been clearly defined. Hypertension is a well-established risk factor for erectile dysfunction, but its relation to testicular damage and male fertility is not clearly understood. This study evaluates the testicular morphology and some spermatozoid parameters of spontaneously hypertensive rats (SHR) untreated and treated with enalapril. SHR rats were assigned into two groups, a hypertensive group (H), and an enalapril treated group (HE). Wistar-Kyoto rats (WKY) were used as controls. Systolic blood pressure was measured weekly until at the end of the experiment. The spermatozoid concentration, motility and viability were determined in epididimal tail collected sample. Stereological methods were used to analyze testicular morphology macroscopically and microscopically. Data were analyzed by one-way ANOVA and Tukeys post test, considering p<0.05. At the end of the experiment systolic blood pressure in the HE group (153,9 mmHg 21,03 ) was similar to WKY animals (153,4 24,41), and lower than H animals (205,1 24,9). Sperm concentration of the H group (1,31 x 107 sptz/ml 0,27) was lower than WKY group (2,11 x 107 sptz/ml 0,34). The blood pressure control with enalapril improved this parameter and HE group (2,46 x 107 sptz/ml 0,54) was similar to WKY. Testicular vascular volumetric density was also higher in hypertensive group while HE animals were similar to controls. The seminiferous epithelium of HE animals showed the highest volumetric density, indicating a possible positive indirect effect of enalapril in spermatogenesis. In this animal model, hypertension promoted morphological changes in the testicle with consequences on spermatozoid production. The blood pressure control with enalapril protected the testicle from these alterations, restoring normal spermatozoid production.

Made available in DSpace on 2014-06-11T19:23:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-25Bitstream added on 2014-06-13T18:50:43Z : No. of bitstreams: 1 cezar_mdm_me_botfm.pdf: 590654 bytes, checksum: 33eb8534bd0be27d262392bb6adb637d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A hipertensão arterial sistêmica é uma das principais causas de insuficiência cardíada (IC). No processo do desenvolvimento da hipertrofia miocárdica e a evolução pra IC, decorrente da sobrecarga pressórica, a ativação dos sistemas nervoso simpático e renina-angiotensina-aldosterona exerce papel fundamental, e a aldosterona tem sido responsabilizada por muitos desses efeitos. Diversos estudos clínicos e experimentais mostraram que o bloqueio da aldosterona atenua a remodelação ventricular na IC avançada. Considerando os efeitos adversos da aldosterona, o bloqueio de seus receptores, na fase mais precoce ao desenvolvimento da IC, poderá ser também benéfico atenuando a progressão da remodelação cardíaca. Para investigar essa questão, foram utilizados ratos espontaneamente hipertensos, com 16 meses de idade, divididos em dois grupos experimentais: controle (CTL) e tratado com espironolactona 20 mg/kg/dia (ESP) por seis meses. A pressão arterial sistólica (PAS) foi medida no início e no final do experimento. A avaliação estrutural e funcional cardíaca in vivo foi realizada por ecocardiograma. O estudo funcional in vitro foi realizado pela técnica do músculo papilar do ventrículo esquerdo (VE). A reserva contrátil foi avaliada após o aumento da concentração de cálcio extracelular, contração pós-pausa e estimulação por β-agonista isoproterenol. Para análise estrutural in vitro foram medidos os pesos do VE, ventrículo direito, átrios, pulmão e amostra de fígado, e calculada a razão peso úmido/peso seco desses órgãos. Amostras do VE foram obtidas para análise histológica, com a finalidade de medira área seccional dos cardiomiócitos (hematoxilina e eosina) e a área ocupada pelo colágeno (picrosirius red), para quantificação de hidroxiprolina e realização da técnica do RT-PCR em tempo real... / Arterial hypertension is one of the main causes of heart failure (HF). In the process of myocardial hypertrophy and HF development due to pressure overload, activation of sympathetic nervous system and renin-angiotensin system plays a fundamental role. Several clinical and experimental studies have been shown that aldosterone blockade attenuates ventricular remodeling in advanced HF. Considering the aldosterone deleterious effects, we hypothesized that the blockade of its receptors in the early phase of HF development can attenuate the progression of cardiac remodeling. To investigate this issue, 16 month-old spontaneously hypertensive rats were used. Rats were separated into two groups: control (CTL) and spironolactone treated (SPR, 20 mg/kg/day) for six months. Systolic arterial pressure (SAP) was measured at the beginning and the end of the experiment. In vivo cardiac structural and functional evaluation was performed by echocardiogram. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscles under isometric contractions. Contractiel reserve was evaluated after extracellular calcium concentration increase, post-pause contractions, and β-agonist isoproterenol stimulation. In vitro structural analysis was done bay measuring LV, right ventricle, and atria weight, and the wet-to-dry weight ratio of these organs and also lung and liver samples. LV samples were stored for histological analysis (cardiomyocyte cross-sectional area and myocardial collagen fraction), measurement of hydroxyproline concentration, and quantification of gene expression of proteins related to cardiac remodeling by real-time RT-PCR. According to sample distribution, normal or non-normal, Student's t test or Mann-Whitney test was used to compare the groups. Mortality rate was analyzed by log-rank test (Kaplan Meier curve). Statistical analysis... (Complete abstract click electronic access below)