Captopril augments both basal and frusemide-induced natriuresis in normal man by suppression of circulating angiotensin II.
1. We studied the renal effects of reinfusing low dose angiotensin II (1 ng kg-1 min-1) into seven salt-replete healthy volunteers after pretreatment with the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg) to establish whether the natriuretic and renal haemodynamic responses to ACE inhibition in normal man result from suppression of circulating angiotensin II. In the same subjects we also studied the effect of captopril (25 mg) with and without exogenous angiotensin II (1 ng kg-1 min-1) on the natriuretic response to intravenous frusemide (20 mg). 2. In the pre-frusemide study captopril increased absolute and fractional excretion of sodium and paraaminohippurate clearance but had no effect on inulin clearance. 3. Reinfusion of angiotensin II after captopril pretreatment completely suppressed the renal effects of ACE inhibition, yielding renal vasoconstrictor and antinatriuretic effects equivalent to those produced by infused angiotensin II in the absence of captopril. 4. Frusemide increased renal sodium excretion without affecting paraaminohippurate or inulin clearance. Captopril augmented frusemide-induced natriuresis and again this effect was reversed by angiotensin II reinfusion. 5. We conclude that captopril augments both basal and frusemide-induced renal sodium excretion in normal man. Our findings suggest that these renal responses to ACE inhibition may be mediated by inhibition of circulating angiotensin II, specifically its renal tubular salt-retaining actions, rather than via effects on other neurohumoral systems.
Motwani
J G
JG
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Struthers
A D
AD
D000284:Administration, Oral; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011897:Random Allocation; D012964:Sodium / Q000652:urine
D000804:Angiotensin II; D005665:Furosemide; D002216:Captopril; D012964:Sodium