RESUMO

In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin-angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1 R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1 R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1 R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal-associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO-AT1 R signalling in the control of refeeding-induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.

Assuntos

Jejum , Órgão Subfornical , Animais , Masculino , Ratos , Angiotensina II/farmacologia , Encéfalo/metabolismo , Jejum/metabolismo , Losartan/farmacologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Órgão Subfornical/metabolismo

RESUMO

INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p < 0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p < 0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1 × 10⁻6 M)- or potassium chloride (8 × 10⁻² M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1 × 10⁻6 - 1 × 10⁻¹ g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5 × 10⁻³ and 5.0 × 10⁻³ g/ml butanolic fraction, the contractions induced by phenylephrine (1 × 10⁻9-3 × 10⁻5 M) and potassium chloride (1 × 10⁻² - 8 × 10⁻² M) were significantly antagonized. The calcium-induced vasocontractions (1 × 10⁻4-1 × 10⁻²M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10⁻² M) medium, as well as in calcium- and potassium-free medium containing 1×10⁻6 M phenylephrine. However, the contractions induced by noradrenaline (1 × 10⁻6 M) and caffeine (4.5 × 10⁻² M) were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

Assuntos

Asteraceae/química , Pressão Sanguínea/efeitos dos fármacos , Butanóis/farmacologia , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Cálcio/análise , Bloqueadores dos Canais de Cálcio/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Folhas de Planta , Potássio/análise , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologia

RESUMO

INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p<0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p<0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1×10-6 M)- or potassium chloride (8×10-2 M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1×10-6-1×10-1 g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5×10-3 and 5.0×10-3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10-9-3×10-5 M) and potassium chloride (1×10-2-8×10-2 M) were significantly antagonized. The calcium-induced vasocontractions (1×10-4-1×10-2 M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10-2 M) medium, as well as in calcium- and potassium-free medium containing 1×10-6 M phenylephrine. However, the contractions induced by noradrenaline (1×10-6 M) and caffeine (4.5×10-2 M) were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

Assuntos

Animais , Masculino , Ratos , Asteraceae/química , Pressão Sanguínea/efeitos dos fármacos , Butanóis/farmacologia , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/análise , Frequência Cardíaca/efeitos dos fármacos , Folhas de Planta , Potássio/análise , Ratos Sprague-Dawley , Vasodilatadores/farmacologia