Insulin resistance plays an intricate role in the development of cardiovascular diseases, hypertension is associated with insulin-resistant states such as diabetes and obesity. However, the underlying mechanism to explain the associations between hypertension and insulin resistance is unknown. The insulin exerts various biological effects in different type of cells. Clinical studies have reported that insulin has been shown to stimulate the protein kinase Akt via activation of PI3K in endothelial cells. Furthermore, insulin stimulated production of nitric oxide (NO) is inhibited by wortmannin in human umbilical vein endothelial cells (HUVECs). We also reported previously that NO contributes to the regulation of blood pressure in central nervous system. The aim of this study was to elucidate the potential mechanisms linking hypertension with insulin resistance and whether insulin signaling may involved in cardiovascular regulation in rat NTS neurons, we investigated the cardiovascular effects of insulin in the nucleus tractus solitarii (NTS) of urethane-anesthetized male spontaneous hypertensive rat (SHR) and normotensive Wistar-kyoto rats (WKY). Unilateral microinjection of insulin (100 IU/ml) into the NTS produced prominent depressor and bradycardic effects in 8/16 week-old WKY. However, no significant cardiovascular effects were found in adult SHR (16 week-old) after insulin injection. Furthermore, young SHR (8 week-old) with normal blood pressure showed depressor and bradycardic effects after insulin injection. Pretreatment with PI3K inhibitor LY294002 and NO synthase inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by insulin in WKY and young SHR but not in adult SHR. Furthermore, insulin induced Akt phosphorylation in-situ in WKY and SHR rats. Thus, these results indicated that insulin-PI3K-Akt-NOS sensitive mechanisms were involved in WKY and young SHR (normotensive) but not in adult SHR (hypertensive). The results also suggested the possible defective insulin signaling may resulted in the development of hypertension in adult SHR.

Cardiovascular disease (CVD) is ranked as one of top leading causes of death in most industrialized countries. Recent research suggests that fruit vinegar beverages (FVB) possess beneficial effects such as antihypertensive properties, reduction of serum cholesterol and triacylglycerols (TAG). FVB made using apple, blueberry, cranberry and tomato were evaluated for their sensory, antioxidant, antihypertensive and lipid lowering properties. All four treatments demonstrated very high in vitro antioxidant and antihypertensive properties. These FVB were further evaluated for their hypolipidemic and antihypertensive properties using a spontaneously hypertensive rats (SHR) model with diet-induced hyperlipidemia. All four FVB significantly reduced serum TAG, elevated the high density lipoprotein (HDL)-cholesterol compared to the control. Further, all four FVB demonstrated a reduction in the diastolic blood pressure after four weeks of supplementation. Overall, the FVB exhibited lipid lowering effects and antihypertensive properties in vivo. Confirmation of the beneficial effects of FVB using a clinical trial is needed.

ABSTRACT The aim of this work was to produce enzymatic hemp seed protein hydrolysates (HPH) followed by bioassay guided fractionation to identify antioxidant and antihypertensive peptides. Therefore, simulated gastrointestinal digestion of isolated hemp seed proteins was conducted using consecutive actions of pepsin and pancreatin to produce HPH, which was then separated by membrane ultrafiltration to obtain peptide sizes of <1, 1-3, 3-5, and 5-10 kDa. Evaluation of HPH and its membrane fractions for antioxidant and antihypertensive properties showed that they significantly (P<0.05) scavenged radicals, reduced and strongly chelated metal ions as well as inhibited lipid oxidation. During a 24-hr test, the HPH reduced systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR) after oral administration by a maximum of -30 mmHg when compared to -15 mmHg for the membrane fractions. To reduce production cost, hemp seed protein meal (HPM) was directly hydrolyzed to a protein hydrolysate (HMH) and was shown to also reduce SBP during 4-8 weeks of dietary feeding. The attenuation of SBP correlated to suppressed plasma levels (0.047-0.059 U/mL and 0.040-0.054 µg/mL) of angiotensin converting enzyme (ACE) and renin, respectively, when compared to the control rats (0.123 U/mL and 0.151 µg/mL). A total of 23 peptides were identified to be present in the HPH. WVYY and PSLPA showed superior in vitro antioxidant properties, while ACE activity was inhibited by WYT (89%), WVYY (91%) and PSLPA (90%). Renin activity was inhibited by WYT (77%), SVYT (87%) and IPAGV (75%). However, oral administration to SHR showed that the pentapeptides (PSLPA and IPAGV) were more effective SBP-reducing agents (-40 mm Hg) when compared to the tri- (-13 mmHg) and tetrapeptides (-36 mmHg). These results show for the first time in literature, the bioactive properties of hemp seed peptides and indicate their potential use as ingredients to formulate antioxidant and antihypertensive functional foods and nutraceuticals.

ABSTRACT The aim of this work was to produce enzymatic hemp seed protein hydrolysates (HPH) followed by bioassay guided fractionation to identify antioxidant and antihypertensive peptides. Therefore, simulated gastrointestinal digestion of isolated hemp seed proteins was conducted using consecutive actions of pepsin and pancreatin to produce HPH, which was then separated by membrane ultrafiltration to obtain peptide sizes of <1, 1-3, 3-5, and 5-10 kDa. Evaluation of HPH and its membrane fractions for antioxidant and antihypertensive properties showed that they significantly (P<0.05) scavenged radicals, reduced and strongly chelated metal ions as well as inhibited lipid oxidation. During a 24-hr test, the HPH reduced systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR) after oral administration by a maximum of -30 mmHg when compared to -15 mmHg for the membrane fractions. To reduce production cost, hemp seed protein meal (HPM) was directly hydrolyzed to a protein hydrolysate (HMH) and was shown to also reduce SBP during 4-8 weeks of dietary feeding. The attenuation of SBP correlated to suppressed plasma levels (0.047-0.059 U/mL and 0.040-0.054 µg/mL) of angiotensin converting enzyme (ACE) and renin, respectively, when compared to the control rats (0.123 U/mL and 0.151 µg/mL). A total of 23 peptides were identified to be present in the HPH. WVYY and PSLPA showed superior in vitro antioxidant properties, while ACE activity was inhibited by WYT (89%), WVYY (91%) and PSLPA (90%). Renin activity was inhibited by WYT (77%), SVYT (87%) and IPAGV (75%). However, oral administration to SHR showed that the pentapeptides (PSLPA and IPAGV) were more effective SBP-reducing agents (-40 mm Hg) when compared to the tri- (-13 mmHg) and tetrapeptides (-36 mmHg). These results show for the first time in literature, the bioactive properties of hemp seed peptides and indicate their potential use as ingredients to formulate antioxidant and antihypertensive functional foods and nutraceuticals.

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.

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.

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

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.

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.

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.