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 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 mumol/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 lower (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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaasjager
K A
KA
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Koomans
H A
HA
Rabelink
T J
TJ
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004573:Electrolytes / Q000652:urine; D004656:Enalapril / Q000494:pharmacology*; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects
D004573:Electrolytes; D016232:Endothelins; D004656:Enalapril; D009543:Nifedipine