Interactions of nifedipine with the renovascular effects of endothelin in humans.
Infusion of endothelin-1 in humans to obtain pathophysiological plasma levels causes mild hypertension, strong sodium retention and renal vasoconstriction. Animal studies have shown that part of these effects depend upon activation of voltage-dependent calcium channels. However, it is unknown whether hemodynamic effects of endothelin-1 in humans, once established, can be reversed by calcium channel blockers. We therefore studied in healthy subjects whether coinfusion of nifedipine, after 60 min of endothelin-1 infusion, could reverse these effects. During endothelin-1 infusion alone, plasma endothelin increased from 2.9 +/- 0.2 to 8.0 +/- 0.6 pmol/l (P < .05). Blood pressure rose by approximately 6 mm Hg at the end of the endothelin-1 infusion (P < .05). Endothelin-1 caused a marked increase in renal vascular resistance by approximately 34% (P < .05) and in filtration fraction by approximately 25% (P < .05). Sodium excretion decreased from a base-line value of 144 +/- 25 to 81 +/- 15 mumol/min at the end of the endothelin infusion (P < .05). During coinfusion of nifedipine, plasma endothelin levels increased to similar values as found during endothelin-1 infusion alone. Blood pressure increase was prevented, whereas the increase in renal vascular resistance and antinatriuresis were reversed completely. However, nifedipine could not reverse the endothelin-induced increase of filtration fraction, indicating that the effects of endothelin-1 and nifedipine in the renal microcirculation do not overlap completely. Because calcium channel blockers have a preferentially preglomerular effect, this suggests that endothelin-1 maintained vasoconstriction of the efferent arteriole in the kidney during nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaasjager
K A
KA
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
van Rijn
H J
HJ
Koomans
H A
HA
Rabelink
T J
TJ
D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D012964:Sodium / Q000652:urine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D016232:Endothelins; D014665:Vasodilator Agents; D012964:Sodium; D009543:Nifedipine