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 dysfunc tion has been investigated by evaluating the effects of the angiotensi n(AT)-converting enzyme inhibition by enalapril. Healthy women were st udied either in normal potassium balance (N3, n=6) or moderate potassi um depletion (KD3, n=6). Potassium depletion (KD) was induced by low p otassium dietary intake (less than or equal to 10 mmol per day) and na triuretic treatment associated with replacement of net NaCl and water losses; the cumulative potassium deficit achieved was 214+/-54 mmol. T he renal function and the urinary excretions of some prostanoids (PGE( 2), 6-keto-PGF(1 alpha), TxB(2)) were evaluated during hypotonic polyu ria (oral water load) and subsequent moderate antidiuresis (lysine-8-v asopressin (LVP) low-dose infusion). Paired studies were performed in absence (control) and presence of enalapril. Basal plasma renin activi ty (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 creatini ne clearance, depression of the diuretic response to water load, inhib ition of distal fractional chloride reabsorption, and blunted efficacy of LVP in increasing the urinary solute concentration. The urinary pr ostanoid excretions were reduced. Basal urinary aldosterone excretion was not changed significantly. In KD3 group enalapril decreased mean a rterial pressure (MAP), increased the plasma potassium concentration, improved the diuretic response to water load and corrected the impairm ent of the distal fractional chloride reabsorption. Despite the decrea se in MAP enalapril did not affect significantly the creatinine cleara nce. Neither urinary prostanoid excretions nor the renal response to L VP were affected by the drug. The data suggest that in KD the increase d activity of the renin-angiotensin system affected the renal function both through direct effects and through effects dependent on the angi otensin-supported secretions of aldosterone and probably of vasopressi n. Finally, by comparing the effects of enalapril and indomethacin in experimental groups with an equivalent degree of KD, evidence is provi ded in favour of the interaction between renin-angiotensin and prostan oid systems in controlling the glomerular filtration rate and the salt and water handling by renal tubules.