The natriuretic effect of the dihydropyridine calcium antagonist felodipine: a placebo-controlled study involving intravenous angiotensin II in normotensive volunteers.
Changes in systemic and renal hemodynamics and in the renin-angiotensin system caused by infusion of the calcium antagonist felodipine were investigated in a placebo-controlled study with 12 normotensive volunteers before and during a graded infusion of angiotensin II (AII). In spite of a fall in blood pressure through vasodilatation, felodipine had a natriuretic effect. There was only a transient rise in effective renal plasma flow (ERPF), whereas glomerular filtration rate (GFR) did not change. Urinary sodium excretion remained elevated when ERPF had normalized. Urinary potassium excretion did not change. AII-induced reductions in ERPF, GFR, and sodium excretion were abolished by felodipine. Felodipine also partly antagonized the rise in plasma aldosterone levels caused by AII. We conclude that the natriuretic effect of dihydropyridine calcium antagonists is probably not caused by a single mechanism, but may be dependent on changes in renal hemodynamics together with a diminished sodium reabsorption at multiple tubular sites. Interference with AII-mediated renal mechanisms and an impairment of the action of aldosterone may contribute to this natriuretic effect as well.
Sluiter
H E
HE
Department of Medicine, Sint Radboud University Hospital, Nijmegen, The Netherlands.
Wetzels
J F
JF
Huysmans
F T
FT
Koene
R A
RA
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology*; D015736:Felodipine; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009568:Nitrendipine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D010919:Placebos; D014655:Vascular Resistance
D002121:Calcium Channel Blockers; D010919:Placebos; D000804:Angiotensin II; D009568:Nitrendipine; D015736:Felodipine