Effects of angiotensin-converting enzyme inhibition on renal dysfunction induced by moderate potassium depletion in healthy women.
The role of the renin-angiotensin system in renal hypokalaemic dysfunction has been investigated by evaluating the effects of the angiotensin (AT)-converting enzyme inhibition by enalapril. Healthy women were studied either in normal potassium balance (N3, n = 6) or moderate potassium depletion (KD3, n = 6). Potassium depletion (KD) was induced by low potassium dietary intake (greater than or equal to 10 mmol per day) and natriuretic treatment associated with replacement of net NaCl and water losses; the cumulative potassium deficit achieved was 214 +/- 54 mmol. The renal function and the urinary excretions of some prostanoids (PGE2, 6-keto-PGF1 alpha, TxB2) were evaluated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis (lysine-8-vasopressin (LVP) low-dose infusion). Paired studies were performed in absence (control) and presence of enalapril. Basal plasma renin activity (PRA) and urinary aldosterone excretion were determined before the water load of control studies. Renal dysfunction typical of chronic KD occurred in the KD3 group, i.e. increase in PRA, decrease in creatinine clearance, depression of the diuretic response to water load, inhibition of distal fractional chloride reabsorption, and blunted efficacy of LVP in increasing the urinary solute concentration. The urinary prostanoid excretions were reduced. Basal urinary aldosterone excretion was not changed significantly. In KD3 group enalapril decreased mean arterial pressure (MAP), increased the plasma potassium concentration, improved the diuretic response to water load and corrected the impairment of the distal fractional chloride reabsorption. Despite the decrease in MAP enalapril did not affect significantly the creatinine clearance. Neither urinary prostanoid excretions nor the renal response to LVP were affected by the drug. The data suggest that in KD the increased activity of the renin-angiotensin system affected the renal function both through direct effects and through effects dependent on the angiotensin-supported secretions of aldosterone and probably of vasopressin. Finally, by comparing the effects of enalapril and indomethacin in experimental groups with an equivalent degree of KD, evidence is provided in favour of the interaction between renin-angiotensin and prostanoid systems in controlling the glomerular filtration rate and the salt and water handling by renal tubules.
Agnoli
G C
GC
Cattedra di Medicina Interna, Università, Bologna, Italy.
Borgatti
R
R
Cacciari
M
M
Ikonomu
E
E
Lenzi
P
P
Marinelli
M
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007677:Kidney Function Tests; D008236:Lypressin / Q000494:pharmacology; D008875:Middle Aged; D011191:Potassium Deficiency / Q000503:physiopathology*; D011453:Prostaglandins / Q000378:metabolism; D011863:Radioimmunoassay; D051437:Renal Insufficiency / Q000188:drug therapy / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D008236:Lypressin; D004656:Enalapril; D007213:Indomethacin