EFFECTIVENESS OF ENALAPRIL VERSUS NIFEDIPINE TO ANTAGONIZE BLOOD-PRESSURE AND THE RENAL RESPONSE TO ENDOTHELIN IN HUMANS

Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and so dium retention. We studied whether oral use of the angiotensin-convert ing enzyme inhibitor enalapril (20 mg BID) or the calcium channel bloc ker nifedipine (60 mg OD) could attenuate these effects of endothelin- 1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. End othelin 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 flo w decreased from 941+/-76 to 729+/-118 mL/min (P<.05) and glomerular f iltration 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); a nd 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. B y contrast, despite renal predilatation, endothelin reduced renal bloo d 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 filtratio n rate fell from 118+/-11 to 108+/-11 mL/min (P<.05). Enalapril did no t alter the antinatriuretic effect of endothelin. Nifedipine did not a ffect blood pressure but prevented the increase caused by endothelin. The endothelin-induced fall in renal blood flow (from 1084+/-100 to 88 8+/-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 f iltration rate was maintained. Nifedipine increased basal sodium excre tion (P<.05), which compensated for the decrease observed during super imposed endothelin infusion. In conclusion, both enalapril and nifedip ine can counteract the hypertensive effect of endothelin, but nifedipi ne is more effective in antagonizing the renal effects of endothelin.