Exogenous aldosterone antagonizes distal tubular effects of calcium entry blocker felodipine.
Calcium entry blockers, such as felodipine, increase natriuresis without increasing kaliuresis. Since these drugs acutely increase plasma renin activity without a concomitant change of aldosterone, inhibition of such stimulated aldosterone release might explain the absence of kaliuresis. In a randomized crossover study in 12 male volunteers, we compared the effects of simultaneously administered exogenous aldosterone and felodipine with the effects of either felodipine or aldosterone alone. Felodipine infusion decreased blood pressure, increased renal plasma flow, and induced natriuresis without kaliuresis. Aldosterone alone reduced sodium excretion and increased potassium excretion without influencing hemodynamics. Addition of aldosterone to felodipine attenuated its natriuretic effect and induced a kaliuresis, which clearly exceeded the rise of potassium excretion during aldosterone alone [delta% fractional excretion of K+ +42 +/- 12 with felodipine+aldosterone and +7 +/- 8% with aldosterone alone; means +/- SE, P < 0.02]. Our data suggest that felodipine-mediated inhibition of stimulated aldosterone release is essential for the absence of kaliuresis with felodipine. In addition, the pronounced kaliuresis with aldosterone during felodipine is in keeping with increased distal sodium delivery due to a proximal tubular action of felodipine.
Van Hamersvelt
H W
HW
Department of Medicine, Sint Radboud Hospital, University of Nijmegen, The Netherlands.
Wetzels
J F
JF
Kloke
H J
HJ
Koene
R A
RA
Huysmans
F T
FT
D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D015736:Felodipine / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007686:Kidney Tubules, Distal / Q000187:drug effects*; D008297:Male; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood
D002121:Calcium Channel Blockers; D004573:Electrolytes; D000450:Aldosterone; D012083:Renin; D015736:Felodipine