Renal synthesis of prostacyclin and thromboxane in the healthy women: differential effects of a short-term saline loading

Abstract

It is accepted that the urinary excretions of the stable metabolites of prostaglandin (PG)I2and thromboxane(Tx) A2, 6-keto-PGF1α(6KPGF) and TxB2respectively, provide an accurate estimate of both basal and stimulated renal synthesis of their precursors. The excretory profile of these metabolites has been evaluated in healthy women submitted to a short-term expansion in extracellular fluid volume. Salt retention (SR group,n =6) was induced by physiological saline (0.9% NaCI) i.v. infusions (2 L per day) over a period of 2 days. On the third day the increase in body weight was 0.92 ± 0.27 kg (P⪡0.05). The results of the study have been compared to those previously obtained in normal balance of sodium and potassium (N group, n=20) and in induced salt depletion (SD group, n=14). A common study protocol was used. Basal values of plasma renin activity (PRA) and urinary aldosterone excretion were determined. Renal functional exploration [clearance (cl.) method] was performed during hypotonic polyuria (induced by oral water load) and subsequent moderate antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue). Urinary 6KPGF and TxB2concentrations were estimated by RIA method and their urinary excretions were determined at both high and low urinary flow rates. The linear regressions of the urinary metabolite excretions vs. urinary flow rate were estimated by using the data obtained in both hypotonic polyuria and antidiuresis. Salt retention (SR vs. N group) was effective in decreasing the basal values of plasma renin activity and urinary aldosterone excretion. Moreover, during hypotonic polyuria it was effective in increasing the absolute and fractional excretions of sodium and chloride, in the absence of significant variations in mean arterial pressure and creatinine cl. Regarding urinary prostanoid excretions the following results were obtained.In conclusion, functionally effective salt retention in healthy women induces a selective stimulation of renal synthesis of prostacyclin, unlike salt depletion, in which the synthesis of both PGI2and TxA2is upregulated.