Systemic and renal haemodynamic effects of angiotensin converting enzyme inhibition by zabicipril in young and in old normal men.
Zabicipril is a recently introduced angiotensin converting enzyme (ACE) inhibitor, which has been observed in experimental animals to increase diuresis, natriuresis, glomerular filtration rate (GFR) and renal plasma flow (RPF). We have investigated the acute effects of zabicipril on systemic and renal haemodynamics in two groups of 8 sodium-replete normal men, aged 23 to 30 y and 65 to 74 y. Zabicipril 0.5 mg, 1 mg or 2.5 mg and a placebo were administered orally, at one week intervals, in a random order and in a double blind fashion. Haemodynamic measurements were performed at base line and every hour for 4 hours after intake of drug or placebo. Cardiac output (Q) was measured by Doppler echography, and RPF and GFR by the constant infusion technique using I123 iodohippurate and Cr51 EDTA, respectively. In the young men zabicipril did not affect Q, heart rate (HR), systemic arterial pressure (AP) or GFR, but it did increase RPF at the 4th hour after the highest dose (from 540 to 653 ml.min-1.m-2). In the old men zabicipril had similar actions, but the effect of the highest dose on RPF (from 355 to 415 ml.min-1.m-2) was less marked than in the young men. In the young and old men the inhibition of ACE peaked at about of 90% or more from the 2th to the 4th hour after the highest dose of zabicipril. We conclude that, in normal men, zabicipril increases the renal fraction of cardiac output in the absence of a concomitant change in systemic haemodynamics. This specific effect of zabicipril on the kidney may be less important with advancing age.
Naeije
R
R
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
Fiasse
A
A
Carlier
E
E
Opsomer
M
M
Leeman
M
M
D000328:Adult; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012079:Renal Circulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C065499:zabicipril