Effects of angiotensin-converting enzyme inhibition on renal adaptations to acute furosemide administration in conscious rats

M Bak, M Shalmi, JS Petersen, LB Poulsen and S Christensen

Department of Pharmacology, University of Copenhagen, Denmark.

During administration of loop diuretics the initial volume depletion activates Na-conserving mechanisms, which reduces glomerular filtration rate (GFR) and stimulates renal tubular reabsorption of Na and water. By i.v. infusion of the angiotensin-converting enzyme inhibitor enalaprilat (100 micrograms bolus; 100 micrograms/h) we examined the role of angiotensin II for the compensatory renal responses occurring during furosemide administration in conscious rats. To evaluate the significance of hydration for the compensatory renal effects of angiotensin II, experiments were performed in groups of rats with or without i.v. replacement of urinary volume losses. Furosemide was administered i.v. (6 mg/kg/h) for 3 1/2 hr. Furosemide infusion produced a short-lasting increase in urine flow rate, Na, Li and K excretion after which the renal excretion rates returned toward pretreatment levels, along with significant reductions in effective renal plasma flow and GFR and increases in effective filtration fraction and effective renal vascular resistance. Sustained increases in urine flow and urinary excretion rates of Na, Li and K were observed in absence of changes in GFR in rats given furosemide with volume replacement. Enalaprilat did not alter the tubular response to furosemide during either euvolemia or volume depletion. However, enalaprilat attenuated the furosemide-induced increases in effective filtration fraction and effective renal vascular resistance. It is concluded that angiotensin II is not essential for the compensatory response of decreased GFR and increased tubular Na reabsorption. However, angiotensin II is an important mediator of renal vasoconstriction during furosemide infusion.

Volume 266, Issue 1, pp. 33-40, 07/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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