Is natriuresis on felodipine due to reversal of the renal effects of angiotensin II?
Felodipine induces natriuresis, possibly by renal hemodynamic and/or tubular effects. Theoretically, reversal of the sodium-retaining effect of angiotensin II (Ang II) could be involved. Therefore, we administered felodipine during Ang II infusion and during suppression of endogenous Ang II production in two double-blind studies in healthy volunteers. First, a gradually increasing dose of Ang II was infused during felodipine or solvent infusion. Before starting Ang II, felodipine had lowered renal vascular resistance (RVR) and filtration fraction (FF), and simultaneously increased CNa. The Ang II induced rise of mean arterial pressure (MAP) and renal vasoconstriction was partly antagonized and the falls in glomerular filtration rate (GFR) and CNa completely abolished by felodipine. The combination of felodipine and 3.0 ng/kg/min Ang II even enhanced natriuresis. Second, felodipine or solvent was infused after one week of pretreatment with placebo or the angiotensin converting enzyme (ACE) inhibitor ramipril, which reduced MAP and induced renal vasodilatation. Ramipril pretreatment did not influence significantly the blood pressure reduction, renal vasodilatation, and natriuresis caused by felodipine. In conclusion, it seems unlikely that the natriuretic effect of felodipine is due to interference with renal effects of endogenous Ang II. The fact that felodipine reverses sodium retention on exogenous Ang II may be explained by interference with systemic and renal hemodynamic effects of exogenous Ang II.
van Hamersvelt
H W
HW
Department of Medicine, Sint Radboud Hospital, University of Nijmegen, The Netherlands.
Sluiter
H E
HE
Wetzels
J F
JF
Koene
R A
RA
Huysmans
F T
FT
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004311:Double-Blind Method; D015736:Felodipine / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D017257:Ramipril
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D000804:Angiotensin II; D017257:Ramipril; D015736:Felodipine