Angiotensin converting enzyme inhibition does not prevent the natriuretic effect of felodipine.
The mechanism of natriuresis with calcium entry blockers such as felodipine is largely unexplained. As these drugs prevent sodium retention following exogenous angiotensin II, the natriuretic effect of felodipine might be due to a similar interaction with endogenous angiotensin II. In such a case, angiotensin converting enzyme inhibition with ramipril should prevent natriuresis with felodipine. We tested this hypothesis in a randomized, double-blind, crossover study in 12 male volunteers by comparing intravenous felodipine after 1 week of oral ramipril with felodipine after placebo and with solvent after ramipril. Ramipril pretreatment reduced ACE activity to 11 +/- 1%, lowered the blood pressure, and increased renal blood flow. However, ramipril pretreatment did not prevent the pronounced increase in natriuresis and diuresis with felodipine. Fractional sodium excretion only tended to increase less during felodipine after ramipril than during felodipine after placebo (absolute changes of + 1.2 +/- 0.2 and + 1.7 +/- 0.2%, respectively; p = 0.07). Ramipril did not influence the felodipine-mediated blood pressure reduction and renal vasodilation. In conclusion, ACE inhibition has no significant effect on the natriuretic and hemodynamic effects of felodipine, suggesting that mechanisms other than interaction with endogenous angiotensin II are involved in these effects of calcium entry blockers.
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; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002712:Chlorides / Q000652:urine; D004311:Double-Blind Method; D015736:Felodipine / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D017257:Ramipril / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D012964:Sodium; D017257:Ramipril; D015736:Felodipine; D011188:Potassium