RESUMO

The aim of this study was to investigate the pharmacological effects of discretamine, an isoquinoline alkaloid isolated from Duguetia magnolioidea Maas, on the cardiovascular system, using a combined in vivo and in vitro approach. Blood pressure and heart rate measurements, as well as changes in isometric tension in rat superior mesenteric arterial rings, elicited by discretamine were recorded. In normotensive non-anaesthetized rats (n = 6), discretamine (0.01; 0.05; 0.1; 0.5; 1, 5 and 10 mg/kg i.v., randomly) injections produced hypotension (-5.2 +/- 1.7; -5.1 +/- 2.1; -7.7 +/- 2; -8.9 +/- 1.7; -9.6 +/- 2.2; -16.8 +/- 2.8 and -13.4 +/- 1.3 mmHg, respectively) accompanied by tachycardia (24.2 +/- 6.1; 36.8 +/- 11.3; 44.2 +/- 7.7; 45.9 +/- 6.4; 48.2 +/- 9.1; 72.1 +/- 14.5 and 64 +/- 17 bpm, respectively). Hypotensive and tachycardic responses were significantly attenuated after L-NAME (20 mg/kg, i.v.) administration. In isolated rat mesenteric artery rings, with endothelium intact, discretamine (10(-12) - 10(-5) M) induced concentration-dependent relaxation of the contractions induced by phenylephrine (10 microM) [pD2 = 6.8 +/- 0.1]. The effect of the discretamine on phenylephrine induced contractions was significantly attenuated after removal of the vascular endothelium [pD2 = 5.8 +/- 0.04]. Similar results were obtained after pre-treatment with L-NAME 100 microM [pD2 = 5.8 +/- 0.04], L-NAME 300 microM [pD2 = 5.9 +/- 0.06], Hydroxocobalamin 30 microM [pD2 = 5.8 +/- 0.06] or ODQ 10 microM [pD2 = 5.8 +/- 0.04]. In addition, in rabbit aorta endothelial cell line, discretamine significantly increased NO3- levels. These results suggest that the hypotensive effect induced by discretamine is probably due to a peripheral vasodilatation, at least, in part, due to the release of NO from vascular endothelium and consequent activation of soluble guanylyl cyclase (GC) in the vascular smooth muscle cells.

Assuntos

Anti-Hipertensivos/farmacologia , Alcaloides de Berberina/farmacologia , Endotélio Vascular/fisiologia , Fatores Relaxantes Dependentes do Endotélio/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Coelhos , Ratos , Ratos Wistar

RESUMO

The cardiovascular effects induced by the aqueous fraction of the ethanol extract of the stem (AFS) of Solanum stipulaceum Roem. & Schult were studied in rats. In non-anesthetized rats, AFS injections produced significant and dosedependent hypotension associated with increase in heart rate. In isolated rat superior mesenteric rings, AFS was able to antagonize the contractions induced by phenylephrine and KCl. The vasorelaxant activity of AFS was not inhibited by either removal of vascular endothelium, L-NAME, atropine or indomethacine. In isolated rat atrial preparations, AFS produced concentration-related negative inotropic and chronotropic responses. These results suggest that the hypotensive effect of AFS is due to a peripheral vasodilation, which can not be attributed to the participation of vascular endothelium. Finally, AFS acts directly on the heart decreasing contractility and heart rate.