Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve activities in rats.

Adenosine is the first drug of choice in the treatment of supraventricular arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA) have been investigated, no information is available on the effects on cardiac vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA and cardiovascular variables to intravenous bolus administration of adenosine. In 34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic fibres were recorded together with ECG, arterial pressure and ventilation, before and after administration of three doses of adenosine (100, 500 and 1000 µg kg(-1)). The effects of adenosine were also assessed in isolated perfused hearts (n = 5). Adenosine induced marked bradycardia and hypotension, associated with a significant dose-dependent increase in VNA (+204 ± 56%, P < 0.01; +275 ± 120%, P < 0.01; and +372 ± 78%, P < 0.01, for the three doses, respectively; n = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted the adenosine-induced bradycardia (-56.0 ± 4.5%, P < 0.05; -86.2 ± 10.5%, P < 0.01; and -34.3 ± 9.7%, P < 0.01, respectively). Likewise, adenosine-induced bradycardia was markedly less in isolated heart preparations. Previous barodenervation did not modify the effects of adenosine on VNA. On the SNA side, adenosine administration was associated with a dose-dependent biphasic response, including overactivation in the first few seconds followed by a later profound SNA reduction. Earliest sympathetic activation was abolished by barodenervation, while subsequent sympathetic withdrawal was affected neither by baro- nor by chemodenervation. This is the first demonstration that acute adenosine is able to activate cardiac VNA, possibly through a central action. This increase in vagal outflow could make an important contribution to the antiarrhythmic action of this substance.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP.

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.

Perinatal salt restriction: a new pathway to programming insulin resistance and dyslipidemia in adult wistar rats.

Several studies support the hypothesis that chronic diseases in adulthood might be triggered by events that occur during fetal development. This study examined the consequences of perinatal salt intake on blood pressure (BP) and carbohydrate and lipid metabolism in adult offspring of dams on high-salt [HSD; 8% (HSD2) or 4% (HSD1)], normal-salt (NSD; 1.3%), or low-salt (LSD; 0.15% NaCl) diet during pregnancy and lactation. At 12 wk of age, female Wistar rats were matched with adult male rats that were fed NSD. Weekly tail-cuff BP measurements were performed before, during, and after pregnancy. After weaning, the offspring received only NSD and were housed in metabolic cages for 24-h urine collection for sodium and potassium and nitrate and nitrite excretion measurements. At 12 wk of age, intra-arterial mean BP was measured, a euglycemic-hyperinsulinemic clamp was performed, and plasma lipids and nitrate and nitrite concentrations were determined. Tail-cuff BP was higher during pregnancy in HSD2 and HSD1 than in NSD and LSD dams. Mean BP (mm Hg) was also higher in the offspring of HSD2 (110 +/- 5) and HSD1 (107 +/- 5) compared with NSD (100 +/- 2) and LSD (92 +/- 2). Lower glucose uptake and higher plasma cholesterol and triacylglycerols were observed in male offspring from LSD dams (glucose uptake: HSD2 17 +/- 4, HSD1 15 +/- 3, NSD 11 +/- 3, LSD 4 +/- 1 mg . kg(-1) . min(-1); cholesterol: HSD2 62 +/- 6, HSD1 82 +/- 11, NSD 68 +/- 10, LSD 98 +/- 17 mg/dL; triacylglycerols: HSD2 47 +/- 15, HSD1 49 +/- 12, NSD 56 +/- 19, LSD 83 +/- 11 mg/dL). In conclusion, maternal salt intake during pregnancy and lactation has long-term influences on arterial pressure, insulin sensitivity, and plasma lipids of the adult offspring.

Papel do bulbo ventrolateral na manutençäo da hipertensäo arterial experimental / Role of rostral ventrolateral medulla in the maintenance of experimental hypertension

o presente trabalho mostra que a integridade funcional da região rostroventrolateral (RVL) é fundamental para a manutenção da pressão arterial (PA) elevada em dois modelos experimentais de hipertensão arterial - dois rins-um clipe (2K, lC) e hipertensão por bloqueio crônico (uma semana) da síntese de óxido nítrico (NO) através da administração de L-Name (70 mg/kg/dia, oral). A inibição bilateral da região RVL através da microinjeção de glicina produziu queda da PA em todos os grupos estudados, porém, de forma diferenciada. Enquanto, no grupo hipertenso renovascular houve normalização da PA, no grupo tratado com L-Name a microinjeção de glicina produziu queda da PA para níveis considerados espinais agudos, da mesma forma que o observado no grupo controle normotenso. Em todos os grupos, o nível de PA atingido pós-glicina não foi diferente do observado em resposta ao bloqueio total do sistema simpático pela administração intravenosa de hexametônio, mostrando que todo o tono vasomotor simpático é proveniente da região RVL. A estimularão da região RVL através da microinjeção de L-glutamato produziu aumento da PA em todos os grupos estudados também de forma diferenciada. No grupo hipertenso renovascular houve pronunciado aumento de PA quando comparado com os animais hipertensos por bloqueio da síntese de NO ou animais normotensos. O bloqueio de receptores glutamatérgicos RVL através da microinjeção de ácido quinurênico produziu queda da PA somente nos animais hipertensos renovasculares, não houve alterações de PA no grupo controle ou tratado com L-Name. O nível de PA atingido pós- ácido quinurênico no grupo hipertenso renovascular não foi diferente daquele obtido após microinjeção de glicina, ou administração de hexamentônio. O bloqueio de receptores angiotensinérgicos RVL através da microinjeção de sartran, produziu queda da PA em todos os grupos, porém, de forma diferenciada. No grupo hipertenso renovascular e normotenso o nível de PA atingido após o bloqueio angiotensinérgico foi semelhante ao nível obtido pós-glicina ou hexametônio. No grupo hipertenso por bloqueio da síntese de NO a queda em resposta ao bloqueio angiotensinérgico foi menos intensa, sugerindo, que neste grupo, os receptores angiotensinérgicos RVL são menos tônicos. O bloqueio de receptores angiotensinérgicos do tipo AT1 RVL, através da microinjeção de Losartan, não produziu queda da PA em nenhum grupo estudado. Em conclusão, apesar da região RVL participar na ...(au)

Evaluation of acute administration of natural products with potential diuretic effects, in humans

In order to evaluate the potential diuretic effect of two natural products, Elephantopus scaber and Alpinia speciosa, a trial administration was carried out in ten healthy volunteers and the effects compared to the those of a placebo. The substances were given on different days, with a seven day interval between doses. The amount of substance administered to the subjects was five times the usual dose i.e. 7.5 g/100 ml and 0.8 g/100 ml respectively. The following parameters parameteres were measured: urinary and plasma sodium, potassium, uric acid, calcium, phosphate, urea, creatinine. The subjects were also examined clinically and total urinary volume was assessed. The only significant finding (p < 0.05) was a slight diuresis with Alpinia speciosa, which also lowered the diastolic (p < 0.05) and systolic (p < 0.01) blood pressures. No effect on electrolytes or renal function parameters was observed, and this probably excludes any renal tubular or glomerular effect from these substances. .