Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and sodium retention. We studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. Endothelin infusion alone increased plasma endothelin from 3.0+/-0.3 to 8.8+/-1.0 pmol/L (P<.05). Blood pressure rose by approximately 6 mm Hg (P<.05). Renal function changes were relatively large: Renal blood flow decreased from 941+/-76 to 729+/-118 mL/min (P<.05) and glomerular filtration rate from 105+/-9 to 92+/-10 mL/min (P<.05); renal vascular resistance increased from 101+/-7 to 152+/-20 mm Hg . min/L (P<.05); and sodium excretion decreased from 158+/-54 to 86+/-27 mu mol/min (P<.05). Enalapril treatment reduced blood pressure from 94+/-2 to 87+/-3 mm Hg (P<.05) and prevented the hypertensive response to endothelin. By contrast, despite renal predilatation, endothelin reduced renal blood flow strongly (from 1063+/-127 to 763+/-100 mL/min, P<.05), although maximal renal vascular resistance was numerically tower (124+/-11 mm Hg . min/L) than during endothelin alone (P<.05). Glomerular filtration rate fell from 118+/-11 to 108+/-11 mL/min (P<.05). Enalapril did not alter the antinatriuretic effect of endothelin. Nifedipine did not affect blood pressure but prevented the increase caused by endothelin. The endothelin-induced fall in renal blood flow (from 1084+/-100 to 888+/-65 mL/min, P<.05) was less than during endothelin infusion alone (P<.05), and maximal renal vascular resistance (111+/-7 mm Hg . min/L) was lower than in both other experiments (P<.05), whereas glomerular filtration rate was maintained. Nifedipine increased basal sodium excretion (P<.05), which compensated for the decrease observed during superimposed endothelin infusion. In conclusion, both enalapril and nifedipine can counteract the hypertensive effect of endothelin, but nifedipine is more effective in antagonizing the renal effects of endothelin.
