Agostinho Tavares

Role of Bradykinin in Insulin Sensitivity and Blood Pressure Regulation During Hyperinsulinemia

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.

Role of Substance P in Blood Pressure Regulation in Salt-Dependent Experimental Hypertension

The participation of substance P in the pathogenesis of five models of experimental hypertension, ie, DOCA-salt, subtotal nephrectomy, one-kidney-one clip renovascular, two-kidney-one clip renovascular, and spontaneous hypertension, was evaluated via an acute infusion of a newly synthesized potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt, subtotal nephrectomy, and one-kidney-one clip renovascular hypertensive rats but only small and nonsignificant changes in blood pressure of two-kidney-one clip renovascular and spontaneously hypertensive rats. CP 96,345 had no effect on the blood pressure of sham-treated controls and Wistar-Kyoto rats. This NK-1 receptor antagonist did not significantly affect the heart rate of any experimental model studied. The data suggest that endogenous substance P may act as a partial counterregulatory mechanism against vasoconstriction in models of salt-dependent hypertension.

Sleep-disordered breathing changes after kidney transplantation:a polysomnographic study

BACKGROUND Sleep disorders are common in patients with end-stage renal disease (ESRD) and are not improved by either conventional haemodialysis or peritoneal dialysis. Sleep-disordered breathing (SDB) is associated with cardiovascular disease and contributes to high mortality found in patients with ESRD. Cure of SDB after transplantation has been anecdotally reported. METHODS Thirty-four non-diabetic patients with ESRD were studied, and clinical, laboratory test and polysomnographic features were determined and compared prior to and after transplantation and between groups with or without SDB, defined as having an apnoea-hypopnoea index (AHI) >or=5. RESULTS An AHI >or=5 was present in nine patients (26.5%) prior to and seven (21%) after transplantation, and no significant reduction of mean AHI was found between study phases (5.3 +/- 7.3 vs 3.1 +/- 4.5; P > 0.05). Transplantation was associated with a significant improvement in sleep architecture. CONCLUSIONS Kidney transplantation is associated with an improvement in sleep architecture, but does not cure SDB in all patients.

Cross-sectional Study on Blood Pressure Control in the Department of Nephrology of the Escola Paulista de Medicina - UNIFESP

OBJECTIVE To assess hypertension control rates in a specialized university-affiliated medical department, the influence of sex, diabetes, and obesity on that control, and the strategies for the treatment of hypertension. METHODS We carried out a cross-sectional study with 1,210 patients followed up for at least 6 months. Information was gathered from medical and nursing records and comprised the following data: sex, age, weight, height, abdominal and hip circumferences, blood pressure, and class and number of the antihypertensive drugs prescribed. To assess obesity, we used body mass index and waist/hip ratio. Blood pressure was considered under control when its levels were below 140/90 mmHg. RESULTS The study consisted of 73% females and 27% males. Most females (31.7%) were 50 to 59 years of age, and most males (28.3%) were 60 to 69 years. The blood pressure control rate found was 20.9% for the 1,210 patients and 23.4% for the hypertensive diabetic patients (n=290). Despite the low control rates found, 70% of the patients used 1 or 2 antihypertensive medications. A high prevalence of obesity (38%) was observed, and females had a greater abdominal obesity index than males did (90% vs 82%, p<0.05). Patients with a greater body mass index had less control of blood pressure. CONCLUSION The percentage of hypertensive patients with controlled blood pressure levels was low and was associated with a high prevalence of obesity. These data indicate the need for reviewing the strategies of global treatment for hypertension.

Intima-media thickness evaluation by B-mode ultrasound: Correlation with blood pressure levels and cardiac structures

The aim of this study was to analyze the thickness of the intima-media complex (IMC) using a noninvasive method. The carotid and femoral common arteries were evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52 hypertensive subjects and the thickness of the IMC was tested for correlation with blood pressure, cardiac structures and several clinical and biological parameters. The IMC was thicker in hypertensive than in normotensive subjects (0.67 +/- 0.13 and 0.62 +/- 0.16 vs 0.54 +/- 0.09 and 0.52 +/- 0.11 mm, respectively, P<0.0001). In normotensive patients, the simple linear regression showed significant correlations between IMC and age, body mass index and 24-h systolic blood pressure for both the carotid and femoral arteries. In hypertensives the carotid IMC was correlated with age and 24-h systolic blood pressure while femoral IMC was correlated only with 24-h diastolic blood pressure. Forward stepwise regression showed that age, body mass index and 24-h systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in normotensives. On the other hand, the femoral IMC relationship was influenced by 24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h systolic blood pressure were the most important determinants of carotid IMC (r2 = 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure (r2 = 0.10). There was an association between carotid IMC and echocardiographic findings in normotensives, while in hypertensives only the left posterior wall and interventricular septum were associated with femoral IMC. We conclude that age and blood pressure influence the intima-media thickness, while echocardiographic changes are associated with the IMC.

Conceituação, epidemiologia e prevenção primária

CONCEITUACAO A hipertensao arterial sistemica (HAS) e uma condicao clinica multifatorial caracterizada por niveis elevados e sustentados de pressao arterial (PA). Associa-se frequentemente a alteracoes funcionais e/ou estruturais dos orgaos-alvo (coracao, encefalo, rins e vasos sanguineos) e a alteracoes metabolicas, com consequente aumento do risco de eventos cardiovasculares fatais e nao fatais.1-4 IMPACTO MEDICO E SOCIAL DA HIPERTENSAO ARTERIAL SISTEMICA HIPERTENSAO ARTERIAL SISTEMICA E AS DOENCAS CARDIOVASCULARES NO BRASIL E NO MUNDO A HAS tem alta prevalencia e baixas taxas [...]

Farmacocinética da associação de glucosamina e sulfato de condroitina em humanos sadios do sexo masculino

A osteoartrose e uma doenca cronica das articulacoes que, uma vez instalada, leva seus portadores a uma incapacidade funcional progressiva. Como os proteocondroitins sulfato sao os maiores constituintes das cartilagens, espera-se que com a ingestao de glucosamina e condroitina haja uma melhora das condicoes biologicas desse tecido. Uma vez que nao temos conhecimento de estudo da farmacocinetica da administracao oral dessa associacao em seres humanos, o objetivo deste trabalho foi avalia-la utilizando a associacao entre o sulfato de glucosamina (SG) e o sulfato de condroitina (SC) administrada a dois grupos de doze voluntarios sadios do sexo masculino (grupo I uma capsula de (500 mg SG; 400 mg SC) e grupo II quatro capsulas). Amostras de sangue foram retiradas a intervalos de tempo pre-definidos ate 48 horas pos-dose. O SG e o SC foram dosados no plasma pelo metodo de DMMB (azul de 1,9,dimetildimetileno). A concentracao maxima foi atingida em 2 horas (media ±SE; 0,893±0,093 µg/mL, grupo I e 2,222±0,313 µg/mL, grupo II). As areas sob a curva ate 48 horas foram de 10,803±0,965 µg-hr/mL e 38,776±2,981 µg-hr/mL, respectivamente para os grupos I e II. Os dois grupos apresentaram um segundo pico apos 18 horas, indicando circulacao entero-hepatica. Os nossos resultados indicam que essa associacao e absorvida por via oral por mecanismo saturavel, o que pode facilitar o seu uso em tratamentos clinicos.

Cardiovascular Effects of a Specific Nonpeptide Antagonist of Substance P (NK-1) Receptor in DOCA-Salt Hypertension

The neurotransmitter substance P acts also as a potent vasodilator. Its participation in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt hypertension was evaluated by an acute infusion of a newly synthesized, potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt rats but only small, transient, and nonsignificant rises in blood pressure of sham-treated control rats. The rise in blood pressure was not accompanied by changes in heart rate. Maximal blood pressure increase in DOCA-salt rats was 31.7 +/- 14.8 mm Hg. In a second series of experiments, the hemodynamic effects of this antagonist were evaluated under anesthesia in both DOCA-salt and sham-treated control rats by the thermodilution method. During CP 96,345 infusion, sustained increases in cardiac index and stroke volume and decreases in total peripheral resistance were observed in both DOCA-salt and control rats. In DOCA-salt rats, cardiac index rose by 79.4%, while total peripheral resistance fell by 27.9% of the baseline values. In control rats, the changes were smaller (+27.2% and -22.5%, respectively). Stroke volume changed in parallel to cardiac output in both groups. The data suggest that acute blockade of NK-1 receptors increases blood pressure in DOCA-salt rats mainly by an increase in cardiac output. We conclude that endogenous substance P tends to counteract the DOCA-salt-induced elevation of blood pressure by modulating both cardiac output and peripheral resistance.