EFFECTIVE ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN THE CONTROL OF PROSTANOID SYNTHESIS AND RENAL-FUNCTION IN HEALTHY WOMEN WITH MODERATE SALT DEPLETION

The interaction between moderate salt depletion and urinary excretions of prostanoids (PGE2, 6-keto-PGF(1 alpha) and TxB(2)), as well as the effective role of the activated renin-angiotensin system (RAS), in th e control of renal function and urinary prostanoid excretions have bee n investigated in healthy women. Salt depletion (SD, n=8) was induced by low sodium chloride dietary intake (less than or equal to 60 mmol p er day) and combined treatment with natriuretic and potassium sparing drugs. The cumulative sodium deficit was 381 +/- 155 mmol. The renal f unction and urinary excretion of prostanoids were evaluated during hyp otonic polyuria (oral water load) and subsequent moderate antidiuresis (lysine-8-vasopressin (LVP) low-dose infusion). Basal plasma renin ac tivity (PRA) and urinary aldosterone excretion were determined, before the water load, in both the SD group and control studies in normal ba lance of sodium and potassium (N, n=20). Paired studies were performed in the absence and in the presence of enalapril in the same SD group, as well as in a subgroup, with normal sodium and potassium balance, p reviously studied (N3, n=6). In the SD vs. N group, significantly high er values of PRA and urinary aldosterone excretion were found. The ren al antinatriuretic mechanism was activated and the diuretic response t o water load depressed. During polyuria, the urinary 6-keto-PGF(1 alph a), and TxB(2) excretions were significantly higher, probably reflecti ng an increase in the renal synthesis of their precursors. During the late LVP infusion, the urinary PGE(2) excretion was also significantly increased, in absence of significant differences in urinary now rate. In both SD and N3 groups, enalapril decreased the mean arterial press ure (MAP). Despite the decrease in MAP, not significantly different in SD vs. N3 group, the drug did not significantly affect the creatinine clearance. Also, the urinary prostanoid excretions were not significa ntly affected by enalapril. However, in the SD group, but not in the N 3 group, the drug was effective in significantly decreasing the absolu te and fractional excretions of sodium and chloride. Moreover, the pla sma potassium concentration significantly decreased, despite the concu rrent decrease in urinary potassium excretion. The data suggest that: (1) in salt depletion, the prostanoid release from the renal cortical structures was stimulated; (2) the renal prostanoid synthesis, either activated (sodium depletion) or not (normal sodium and potassium balan ce), was not affected by the RAS pharmacological blockade in the short -term; (3) in salt depletion, the RAS blockade recruited a homeostatic mechanism responsible for the improved renal salt conservation, as we ll as for the redistribution of potassium between the extra- and intra -cellular compartments.