Acute hypotensive effect of diminazene aceturate in spontaneously hypertensive rats: role of NO and Mas receptor.

Diminazene aceturate (DIZE) has been described as an angiotensin-converting enzyme 2 (ACE2) activator. We aimed to investigate DIZE effects on blood pressure (BP) of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. BP was recorded in awake and unrestrained rats 24 hours after femoral artery catheterization. DIZE (15 mg/kg, s.c.) produced a fast BP decrease only in SHR (P < .01). Pre-treatment with L-NAME (10 mg/kg, iv) did not change the hypotensive effect on systolic BP whereas mitigated the DIZE effect on diastolic BP (∆ Emax: -31 ± 5 DIZE vs -15 ± 1 mm Hg DIZE + L-NAME, P < .05). BP changes after DIZE remained unchanged after the treatment of rats with A-779 (50 ug/kg, iv), a Mas receptor blocker. Vasodilatation curves to DIZE (10-9 to 10-4  mol/L) in mesenteric arteries confirmed the NO-mediation on DIZE effects in SHR, as L-NAME (300 µmol/L) reduced the vascular sensitivity (∆EC50: -5.12 ± 0.09 CONTROL vs -4.66 ± 0.08 L-NAME, P < .05) and the magnitude of DIZE effect (area under the curve (AUC), 357.5 ± 8.2 DIZE vs 424.7 ± 11.6 L-NAME; P < .001), whereas A-779 (1 µmol/L) enhanced DIZE response (AUC, 357.5 ± 8.2 DIZE vs 309.8 ± 14.7 A-779, P < .05). Our findings indicate that DIZE acutely reduces the BP in SHR possibly by a mechanism other than Mas receptor activation. This effect seems to be mediated, at least partially, by NO.

Prevalence of cardiovascular risk factors in the population of Vitória according to data from VIGITEL and the National Health Interview Survey of 2013. / Prevalência de fatores de risco cardiovascular na população de Vitória segundo dados do VIGITEL e da Pesquisa Nacional de Saúde de 2013.

OBJECTIVE: To compare the prevalence of cardiovascular risk factors in the adult population of Vitória, Espírito Santo, Brazil, in two surveys conducted by telephone interview (VIGITEL) or by clinic and laboratory exams during the National Health Interview Survey (NHIS). METHOD: Data were collected from adults (≥ 18 years). In VIGITEL, 1,996 subjects (males = 38%) were interviewed. In NHIS, home visit followed by clinical and laboratory tests was made with 318 individuals (males = 48%) selected in 20 census tracts of the city. The prevalence of risk factors was adjusted to the estimated population of the city in 2013. Data are shown as prevalence and 95% confidence interval (95%CI). RESULTS: Similar values of prevalence were found in VIGITEL and NHIS, respectively, for smoking (8.2%; 95%CI 6.7-9.7% vs 10.0; 95%CI 6.4 - 13.6%) and hypertension (24.8%; 95%CI 22.6 - 27.0% vs 27.2%; 95%CI 21.8 - 32.5%). Statistical differences between surveys (p < 0.01) were found for diabetes (6.7%; 95%CI 5.6 - 7.9% vs 10.7%; 95%CI 7.1 - 14.5%), obesity (16.8%; 95%CI 14.1 - 18.1% vs 25.7%; 95%CI 20.4 - 30.9%) and high cholesterol (≥ 200mg/dL) (20.6%; 95%CI 18.6- 22.6% vs 42.3%; 95%CI 36.9 - 47.7%). The prevalence of diabetes was also higher (p < 0.01) in NHIS (6.7 vs 10.7%). CONCLUSION: Prevalence of smoking and hypertension, but not obesity, was adequately detected in VIGITEL, because there might have been information bias related to body weight during telephone interviews. Datashow the necessity to improve the diagnosis of dyslipidemias in primary care services, as the control of this risk factor is of utmost importance to prevent cardiovascular diseases.

OBJETIVO: Comparar a prevalência de fatores de risco cardiovascular na população de Vitória (ES) em pesquisa autorreferida por contato telefônico (VIGITEL) ou por exames clínicos e laboratoriais realizados na Pesquisa Nacional de Saúde (PNS). MÉTODO: Os inquéritos foram realizados na população adulta de Vitória (≥18anos). No VIGITEL foram entrevistados 1996 indivíduos (homens = 38%). Na PNS foi feita visita domiciliar seguida de exames clínicos e laboratoriais em 318 indivíduos (homens = 48%) selecionados em 20setores censitários da cidade. Nos dois inquéritos, as prevalências foram ajustadas para a estrutura populacional estimada para o ano de 2013. Os dados são fornecidos como porcentagens e intervalo de confiança de 95% (IC95%). RESULTADOS: Foram encontradas prevalências similares no VIGITEL e na PNS, respectivamente, para tabagismo (8,2%; IC95% 6,7 - 9,7% versus 10,0; IC95% 6,4 - 13,6%) e hipertensão (24,8%; IC95% 22,6- 27,0% versus 27,2%; IC95% 21,8 - 32,5%). Houve diferença estatística (p < 0,01) entre o VIGITEL e a PNS, respectivamente, para as prevalências de obesidade (16,8%; IC95% 14,1 - 18,1% versus 25,7%; IC95% 20,4- 30,9%) e colesterol elevado (≥ 200mg/dL) no sangue (20,6%; IC95% 18,6 - 22,6% versus 42,3%; IC95% 36,9- 47,7%). A prevalência de diabetes também foi maior (p < 0,05) na PNS (6,7 versus 10,7%). CONCLUSÃO: A prevalência populacional de hipertensão e tabagismo foi estimada adequadamente no VIGITEL. Isso não ocorreu com a obesidade por provável viés de informação do peso corporal no VIGITEL. Os dados mostram a necessidade de melhorar a cobertura diagnóstica das dislipidemias em vista da importância do controle desse fator de risco na prevenção primária das doenças cardiovasculares.

Prevalência de fatores de risco cardiovascular na população de Vitória segundo dados do VIGITEL e da Pesquisa Nacional de Saúde de 2013 / Prevalence of cardiovascular risk factors in the population of Vitória according to data from VIGITEL and the National Health Interview Survey of 2013

RESUMO: Objetivo: Comparar a prevalência de fatores de risco cardiovascular na população de Vitória (ES) em pesquisa autorreferida por contato telefônico (VIGITEL) ou por exames clínicos e laboratoriais realizados na Pesquisa Nacional de Saúde (PNS). Método: Os inquéritos foram realizados na população adulta de Vitória (≥18anos). No VIGITEL foram entrevistados 1996 indivíduos (homens = 38%). Na PNS foi feita visita domiciliar seguida de exames clínicos e laboratoriais em 318 indivíduos (homens = 48%) selecionados em 20setores censitários da cidade. Nos dois inquéritos, as prevalências foram ajustadas para a estrutura populacional estimada para o ano de 2013. Os dados são fornecidos como porcentagens e intervalo de confiança de 95% (IC95%). Resultados: Foram encontradas prevalências similares no VIGITEL e na PNS, respectivamente, para tabagismo (8,2%; IC95% 6,7 - 9,7% versus 10,0; IC95% 6,4 - 13,6%) e hipertensão (24,8%; IC95% 22,6- 27,0% versus 27,2%; IC95% 21,8 - 32,5%). Houve diferença estatística (p < 0,01) entre o VIGITEL e a PNS, respectivamente, para as prevalências de obesidade (16,8%; IC95% 14,1 - 18,1% versus 25,7%; IC95% 20,4- 30,9%) e colesterol elevado (≥ 200mg/dL) no sangue (20,6%; IC95% 18,6 - 22,6% versus 42,3%; IC95% 36,9- 47,7%). A prevalência de diabetes também foi maior (p < 0,05) na PNS (6,7 versus 10,7%). Conclusão: A prevalência populacional de hipertensão e tabagismo foi estimada adequadamente no VIGITEL. Isso não ocorreu com a obesidade por provável viés de informação do peso corporal no VIGITEL. Os dados mostram a necessidade de melhorar a cobertura diagnóstica das dislipidemias em vista da importância do controle desse fator de risco na prevenção primária das doenças cardiovasculares.

ABSTRACT: Objective: To compare the prevalence of cardiovascular risk factors in the adult population of Vitória, Espírito Santo, Brazil, in two surveys conducted by telephone interview (VIGITEL) or by clinic and laboratory exams during the National Health Interview Survey (NHIS). Method: Data were collected from adults (≥ 18 years). In VIGITEL, 1,996 subjects (males = 38%) were interviewed. In NHIS, home visit followed by clinical and laboratory tests was made with 318 individuals (males = 48%) selected in 20 census tracts of the city. The prevalence of risk factors was adjusted to the estimated population of the city in 2013. Data are shown as prevalence and 95% confidence interval (95%CI). Results: Similar values of prevalence were found in VIGITEL and NHIS, respectively, for smoking (8.2%; 95%CI 6.7-9.7% vs 10.0; 95%CI 6.4 - 13.6%) and hypertension (24.8%; 95%CI 22.6 - 27.0% vs 27.2%; 95%CI 21.8 - 32.5%). Statistical differences between surveys (p < 0.01) were found for diabetes (6.7%; 95%CI 5.6 - 7.9% vs 10.7%; 95%CI 7.1 - 14.5%), obesity (16.8%; 95%CI 14.1 - 18.1% vs 25.7%; 95%CI 20.4 - 30.9%) and high cholesterol (≥ 200mg/dL) (20.6%; 95%CI 18.6- 22.6% vs 42.3%; 95%CI 36.9 - 47.7%). The prevalence of diabetes was also higher (p < 0.01) in NHIS (6.7 vs 10.7%). Conclusion: Prevalence of smoking and hypertension, but not obesity, was adequately detected in VIGITEL, because there might have been information bias related to body weight during telephone interviews. Datashow the necessity to improve the diagnosis of dyslipidemias in primary care services, as the control of this risk factor is of utmost importance to prevent cardiovascular diseases.

The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats.

Diminazene aceturate (DIZE) has been reported to enhance the catalytic efficiency of ACE-2 and presumably increases angiotensin 1-7 generation, interfering with cardiac remodeling after myocardial infarction (MI). Our aim was to investigate the chronic effects of DIZE on cardiac dysfunction post-MI. Male Wistar rats underwent myocardial infarction (MI) or SHAM surgery (SO) and were divided into groups treated with DIZE 15 mg/kg/day, s.c. or vehicle (Control). After 4 weeks, the hemodynamic variables were recorded by cardiac catheterism. Hearts were then arrested to obtain the left ventricular (LV) pressure-volume curves in situ. Cardiomyocyte hypertrophy and collagen content were determined by histology. DIZE prevented LV end-diastolic pressure increases in MI rats (MI: 26 ± 3.3 vs. MI-DIZE: 15 ± 1.6 mmHg, P < 0.001) without a significant effect on LV systolic pressure (LVSP). Moreover, DIZE improved LV contractility (+dP/dt, MI: 3014 ± 161 vs. MI-DIZE: 3884 ± 104 mmHg/s, P < 0.001) and relaxation (-dP/dt, MI: -2333 ± 91 vs. MI-DIZE: -2798 ± 120 mmHg/s, P < 0.05). Right ventricular SP was increased in the MI compared to that in the SO group (40 ± 0.6 vs. 30 ± 1.2 mmHg; P < 0.01), and DIZE partially prevented this augmentation. LV stiffness was reduced in MI-DIZE compared with that in MI (0.64 ± 0.01 vs. 0.78 ± 0.02 mmHg/mL; P < 0.01). DIZE treatment reduced the interstitial collagen content by 18% in the surviving LV myocardium. Cardiomyocyte hypertrophy remained unaffected by DIZE treatment. Our findings show that chronic DIZE treatment post-MI attenuates the morphofunctional changes induced by MI in rats. The effects on LV -dP/dt, chamber stiffness and collagen content suggest this drug can be used as a therapeutic agent to reduce interstitial fibrosis and diastolic dysfunction after MI.

Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats.

It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C m) and I to were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I to in the left but not the right ventricle. Both the treated groups restored I to in the left ventricle. However, in the right ventricle, only enalapril treatment modified I to. The SHRE group exhibited a significant increase in I to compared to all the other groups. These findings suggest that enalapril may increase I to by a pressure overload independent mechanism.

Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size.

The electrocardiogram (ECG) has been a useful tool to identify ischemia in humans and laboratory animals. Previous ECG studies showed that presence of pathological Q waves in lead DI in rats submitted to ligature of the left coronary artery (LCA) is a good predictor of successful myocardial infarction (MI). This study aimed to determine the sensitivity and the specificity of these ECG findings to predict successful MI. Male Wistar rats were submitted to surgical ligature of the LCA (N=86) or sham-operation (SO, N=16). ECG was recorded under halothane/ether anesthesia before surgery and 1, 3, 5, 7, and 15 days later. MI was determined by the presence of a transmural fibrous scar. Sixty-nine rats survived and 60 showed fibrous scar indicating a successful production of MI (18 and 42 animals were analyzed 1 or 15 days after MI, respectively). Twenty-four hours after, Q amplitude was linearly related to infarct size (r=-0.778; P<0.01), but not 15 days after (r=-0.416; P>0.05). In 53 out of 60 rats with transmural scar, Q wave in lead DI was identified in the ECG. Absence of Q wave occurred in 7 animals. The sensitivity was 88% (CI(95)=83-93%). Nine animals submitted to coronary ligature did not show infarct scar. One of these animals, however, showed Q wave in DI, indicating a specificity of 77% (CI(95)=65-104%). In conclusion, ECG can be used as a reliable tool to identify MI and can be used to predict the infarct size as earlier as 1 day after LCA ligation in rats.

Correlation between the creatinine clearance in the urine collected during 24 hours and 12 hours.

INTRODUCTION: Creatinine concentration in plasma has been used to evaluate renal function. However, the endogenous creatinine clearance (CrCl) is more sensitive to this goal. OBJECTIVE: Correlate the CrCl calculated from urinary collects of 12 h and 24 h. METHODS: Ninety five volunteers (34-64 y) collected the urine for 24 h into two bottles: night, from 7 am to 7 pm and day, from 6 am to 7 pm. A fasting blood sample was used to measure plasma creatinine. Correlation between variables was determined by Pearson method (r) and the agreement between night and 24 h CrCl was determined by the Bland-Altman plot. RESULTS: Urines of 4 individuals were discarded because of collect errors. In the final sample (n = 91; 42 males), hypertension was found in 23 and diabetic in 5. The CrCl (mL/min/1.73 m²) was slightly lower in females in the night (77.8 ± 22.7 versus 88.4 ± 23.6; p < 0.05) and similar in males (91.2 ± 22.9 versus 97.3 ± 30.9; p > 0.05). Strong correlations were observed between the CrCl calculated from the night and day urines and the 24 h (r = 0.85 and 0.83; respectively). Agreement between the CrCl calculated from night or day urine and the 24 h urine was observed, respectively, to 85 and 83 individuals. CONCLUSION: The 12 h urine, mainly obtained at night, gives CrCl values similar to those obtained in the 24 h collect. Since urine collect is easier to outpatients at night, this period should be chosen in the clinical evaluation of the glomerular filtration rate.

Correlação entre a depuração plasmática de creatinina utilizando urina coletada durante 24 horas e 12 horas / Correlation between the creatinine clearance in the urine collected during 24 hours and 12 hours

INTRODUÇÃO: A concentração da creatinina no plasma é usada para avaliar a função renal, mas a depuração da creatinina plasmática (DCP) constitui método mais sensível para essa finalidade. OBJETIVO : Correlacionar a DCP em coleta urinária de 12 horas noturna com a de 24 horas. MÉTODOS: Noventa e cinco voluntários (34-64 anos) coletaram urina durante 24 horas em dois frascos: diurno (das 7h às 19h) e noturno (das 19h às 7h do dia seguinte). A coleta de sangue se deu em jejum para medidas bioquímicas. A correlação entre as variáveis foi feita pelo teste Pearson (r) e a concordância de medidas, pelo teste de Bland-Altman. RESULTADOS: Urinas de quatro indivíduos foram recusadas por erro de coleta. Na amostra final (n = 91; 42 homens), havia 23 hipertensos e cinco diabéticos. A DCP (mL/min/1,73 m²) foi menor no período noturno em mulheres (77,8 ± 22,7 versus 88,4 ± 23,6; p < 0,05) e similar em homens (91,2 ± 22,9 versus 97,3 ± 30,9; p > 0,05). As correlações entre a DCP na urina de 12 horas noturna ou diurna e a de 24 horas foram fortes (r = 0,85 e 0,83, respectivamente). Em 85 e 83 dos 91 indivíduos, a medida da DCP noturna e diurna, respectivamente, foi concordante com a de 24 horas. CONCLUSÃO: A urina de 12 horas, sobretudo quando coletada à noite, fornece valores de DCP similares àqueles obtidos em coleta de 24 horas. Como essa coleta é mais fácil de ser feita em pacientes ambulatoriais à noite, esse período deveria ser preferido para a medida da filtração glomerular.

INTRODUCTION: Creatinine concentration in plasma has been used to evaluate renal function. However, the endogenous creatinine clearance (CrCl) is more sensitive to this goal. OBJECTIVE : Correlate the CrCl calculated from urinary collects of 12 h and 24 h. METHODS: Ninety five volunteers (34-64 y) collected the urine for 24 h into two bottles: night, from 7 am to 7 pm and day, from 6 am to 7 pm. A fasting blood sample was used to measure plasma creatinine. Correlation between variables was determined by Pearson method (r) and the agreement between night and 24 h CrCl was determined by the Bland-Altman plot. RESULTS: Urines of 4 individuals were discarded because of collect errors. In the final sample (n = 91; 42 males), hypertension was found in 23 and diabetic in 5. The CrCl (mL/min/1.73 m²) was slightly lower in females in the night (77.8 ± 22.7 versus 88.4 ± 23.6; p < 0.05) and similar in males (91.2 ± 22.9 versus 97.3 ± 30.9; p > 0.05). Strong correlations were observed between the CrCl calculated from the night and day urines and the 24 h (r = 0.85 and 0.83; respectively). Agreement between the CrCl calculated from night or day urine and the 24 h urine was observed, respectively, to 85 and 83 individuals. CONCLUSION: The 12 h urine, mainly obtained at night, gives CrCl values similar to those obtained in the 24 h collect. Since urine collect is easier to outpatients at night, this period should be chosen in the clinical evaluation of the glomerular filtration rate.

Cardiac ventricular weights recorded at the autopsy of healthy subjects who died of external causes.

OBJECTIVE: To establish cardiac ventricular weights recorded during the autopsy of healthy individuals who died of external causes, aiming at determining normality patterns in our population. METHODS: A total of 94 hearts were evaluated at the Forensics Department of the city of Vitória, Espírito Santo. After the heart removal and resection of the atria and epicardial fat, the right ventricle (RV) and the left ventricle (LV), including the septum, were separated and weighed and the mass was indexed by the height. The Kolmogorov-Smirnov test was used to test the normality of the distribution. Data are presented as means+/- SD. RESULTS: After the exclusion of 12 hearts (possible cardiovascular disease detected post-mortem) 82 hearts were examined (52 males and 30 females, aged 16-68 yrs, 31+/-12 yrs). The weight of the LV was 181+/-25 g and 125+/-15 g, and the weight of the RV was 54+/-7 g and 38+/-6 g; the LV mass indexed by height was 105+/-14 g/m and 78+/-8 g/m, for males and females, respectively. The P95 of the LV weight was 218 g and 128 g/m in males and 148 g and 88 g/m in females. No significant correlation between ventricular mass and age was observed. CONCLUSION: The weight of the LV in the males from our sample was higher than that reported in the contemporary literature. Our results suggest that the presence of LV hypertrophy can be inferred in the presence of LV mass > 218 g or 128 g/m in males and 148 g or 88 g/m in females.

Peso dos ventrículos cardíacos determinado em necropsia de indivíduos saudáveis mortos por causas externas / Cardiac ventricular weights recorded at the autopsy of healthy subjects who died of external causes

OBJETIVO: Determinar o peso dos ventrículos cardíacos em necropsia de indivíduos sadios vítimas de morte acidental, visando determinar padrões de normalidade em nossa população. MÉTODOS: Foram examinados 94 corações no Instituto Médico Legal de Vitória. Após remoção do coração e ressecção dos átrios e gordura epicárdica, os ventrículos direito (VD) e esquerdo (VE), incluindo o septo, foram separados e pesados e a massa indexada pela altura. O teste de Kolmogorov-Smirnov foi usado para testar normalidade da distribuição. Os dados são apresentados como média ± desvio padrão. RESULTADOS: Após 12 exclusões (doença cardiovascular possível detectada após a morte) foram analisados 82 corações (52 homens e 30 mulheres, 16-68 anos, média 31±12 anos). O peso do VE foi de 181±25 g e 125±15 g, do VD foi de 54±7 g e 38±6 g e a massa de VE indexada pela altura foi de 105±14 g/m e 78±8 g/m para homens e mulheres, respectivamente. O P95 do peso do VE foi de 218 g e 128 g/m em homens e 148 g e 88 g/m em mulheres. Não detectamos correlação significante entre a massa ventricular e idade. CONCLUSÃO: O peso do ventrículo esquerdo do coração dos homens da nossa amostra foi superior aos relatados na literatura contemporânea. Nossos resultados sugerem que a presença de hipertrofia de VE pode ser inferida em presença de massa de VE superior a 218 g ou 128 g/m nos homens e 148 g ou 88 g/m nas mulheres.

OBJECTIVE:To establish cardiac ventricular weights recorded during the autopsy of healthy individuals who died of external causes, aiming at determining normality patterns in our population. METHODS:A total of 94 hearts were evaluated at the Forensics Department of the city of Vitória, Espírito Santo. After the heart removal and resection of the atria and epicardial fat, the right ventricle (RV) and the left ventricle (LV), including the septum, were separated and weighed and the mass was indexed by the height. The Kolmogorov-Smirnov test was used to test the normality of the distribution. Data are presented as means± SD. RESULTS:After the exclusion of 12 hearts (possible cardiovascular disease detected post-mortem) 82 hearts were examined (52 males and 30 females, aged 16-68 yrs, 31±12 yrs). The weight of the LV was 181±25 g and 125±15 g, and the weight of the RV was 54±7 g and 38±6 g; the LV mass indexed by height was 105±14 g/m and 78±8 g/m, for males and females, respectively. The P95 of the LV weight was 218 g and 128 g/m in males and 148 g and 88 g/m in females. No significant correlation between ventricular mass and age was observed. CONCLUSION:The weight of the LV in the males from our sample was higher than that reported in the contemporary literature. Our results suggest that the presence of LV hypertrophy can be inferred in the presence of LV mass > 218 g or 128 g/m in males and 148 g or 88 g/m in females.