Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide.
In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.
Toussaint
C
C
Klinik II, Universität zu Köln, Klinikum Merheim.
Masselink
A
A
Gentges
A
A
Wambach
G
G
Bönner
G
G
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007610:Kallikreins / Q000652:urine*; D007705:Kinins / Q000652:urine*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D006852:Hydrochlorothiazide; D005665:Furosemide; D007610:Kallikreins