Effects of angiotensin-converting enzyme inhibition on renal adaptations to acute furosemide administration in conscious rats.
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.
Department of Pharmacology, University of Copenhagen, Denmark.
M
M
Bak
M
M
Shalmi
J S
JS
Petersen
L B
LB
Poulsen
S
S
Christensen
D000042:Absorption; D000222:Adaptation, Physiological / Q000187:drug effects; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000502:physiology; D003243:Consciousness; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000493:pharmacokinetics; D012996:Solutions; D013997:Time Factors; D014867:Water / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D012996:Solutions; D014867:Water; D000804:Angiotensin II; D005665:Furosemide; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D011188:Potassium