Artículos de revistas
Endothelin-1 attenuates bradykinin-induced hypotension in rats
Registro en:
European Journal Of Pharmacology. Elsevier Science Bv, v. 397, n. 41700, n. 367, n. 371, 2000.
0014-2999
WOS:000087648300018
10.1016/S0014-2999(00)00239-9
Autor
Tanus-Santos, JE
Gordo, WM
Francisco-DoPrado, J
Sampaio, RC
Moreno, H
Institución
Resumen
Endothelin-l has vasoconstrictor and mitogenic properties and may contribute to the pathogenesis of hypertension by enhancing vasoconstrictor mechanisms. In this study, we investigated the ability of endothelin-1 decrease the hypotensive effects of the vasodilator bradykinin in anesthetized rats. We also studied the effects a two-week oral pre-treatment with losartan (10 mg/kg/day) or enalapril (25 mg/kg/day) on endothelin-1-induced changes in the hypotensive responses to bradykinin. Bradykinin (0.4, 1.6, 6.4, and 25 mu g/kg, i.v.) induced dose-dependent hypotensive responses which were attenuated (P < 0.05) by endothelin-1 (2 mu g/kg, i.v.). This effect of endothelin-1 was abolished by the mixed endothelin receptor antagonist N-Acetyl-alpha-[10,11-Dihydro-5H-dibenzo[a, d]cycloheptadien-5-yl]-D-Gly-Leu-Asp-Ile-Ile-Trp (PD145065, 1 mg/kg, i.v.). Endothelin-1 also decreased (P < 0.05) the responses to bradykinin in rats pre-treated with losartan, but had no effect in rats pre-treated with enalapril. These results suggest that endothelin-1 may contribute to the development of hypertension by decreasing the responses to bradykinin through a mechanism not involving angiotensin AT(1) receptors, although the inhibition of angiotensin converting enzyme blunted the effect of endothelin-1. (C) 2000 Elsevier Science B.V. All rights reserved. 397 41700 367 371