Endothelin-1 attenuates bradykinin-induced hypotension in rats.
Endothelin-1 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 mcg/kg, i.v.) induced dose-dependent hypotensive responses which were attenuated (P<0.05) by endothelin-1 (2 mcg/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.
Tanus-Santos
J E
JE
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), P.O. Box 6111, 13081-970, São Paulo, Campinas, Brazil.
Gordo
W M
WM
Francisco-DoPrado
J
J
Sampaio
R C
RC
Moreno
H
H
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D007022:Hypotension / Q000503:physiopathology / Q000517:prevention & control*; D007275:Injections, Intravenous; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D004656:Enalapril; D019808:Losartan; D001920:Bradykinin