Endothelin-1 attenuates bradykinin-induced hypotension in rats

Endothelin-l has vasoconstrictor and mitogenic properties and may contribut e to the pathogenesis of hypertension by enhancing vasoconstrictor mechanis ms. 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 m g/kg/day) or enalapril (25 mg/kg/day) on endothelin-1-induced changes in th e 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 attenu ated (P < 0.05) by endothelin-1 (2 mu g/kg, i.v.). This effect of endotheli n-1 was abolished by the mixed endothelin receptor antagonist N-Acetyl-alph a-[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 effec t in rats pre-treated with enalapril. These results suggest that endothelin -1 may contribute to the development of hypertension by decreasing the resp onses to bradykinin through a mechanism not involving angiotensin AT(1) rec eptors, although the inhibition of angiotensin converting enzyme blunted th e effect of endothelin-1. (C) 2000 Elsevier Science B.V. All rights reserve d.