We attempt to elucidate the putative indirect mechanisms by which endothelin-1 affects mean blood pressure and renal blood flow in normotensive awake rats. Endothelin-1 (700 pg/kg, i.v.) induced a short-lasting decrease followed by a prolonged increase in mean blood pressure (from 113 ± 4 to 92 ± 4 mmHg at 30 sec, 132 ± 7 mmHg at 10 min, and 129 ± 6 mmHg at 30 min, p <0.01), and caused a profound and long-lasting fall in renal blood flow as measured by Doppler flowmeter technique (from 2.87 ± 0.29 to 1.40 ± 0.37 kHz at 30 sec, 1.77 ± 0.32 kHz at 10 min and 2.10 ± 0.45 kHz at 30 min, p <0.01). Neither the receptor antagonist of bradykinin D-Arg0-Hyp3-Thi5,8-DPhe7-bradykinin (30 μg/kg/min, i.v.) nor the antagonist of angiotensin II Sar1,Thr8-angiotensin II (4 μg/kg/min, i.v.) altered the changes in mean blood pressure and renal blood flow induced by endothelin-1. The antagonist of EDRF synthesis, N(G)monomethyl-L-arginine (100 μg/kg/min, i.v.) enhanced the endothelin-1-induced increase in mean blood pressure (endothelin-1: 20 ± 2 mmHg vs endothelin-1 + EDRF antagonist: 39 ± 3 mmHg at 10 min, p <0.01) and decrease in renal blood flow (endothelin-1: -40 ± 4% vs endothelin-1 + EDRF antagonist: -73 ± 3% at 10 min, p <0.01). Enalaprilat (300 μg/kg, i.v.), an inhibitor of the enzyme which converts angiotensin I into angiotensin II and degrades kinins, overrode the systemic and renal hemodynamic effects of endothelin-1. We conclude that stimulation of EDRF release by endothelin-1 can buffer the systemic and renal hemodynamic effects of the latter compound. As the antagonist Sar1,Thr8-angiotensin did not prevent the action of endothelin-1, the mechanism by which enalaprilat protects against endothelin-1-induced vasoconstriction does not appear to be mediated by the blockade of angiotensin II formation.
|Number of pages||7|
|Journal||Clinical and Investigative Medicine|
|Publication status||Published - 1991|
- converting enzyme inhibitors
- renal blood flow
ASJC Scopus subject areas