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

It it is accepted that the urinary excretions of the stable metabolites of prostaglandin (PG)l(2) and thromboxane(Tx) A(2), 6-keto-PGF(1 alpha) (6KPGF ) and TxB(2) respectively, provide an accurate estimate of both basal and s timulated renal synthesis of their precursors, The excretory profile of the se metabolites has been evaluated in healthy women submitted to a short-ter m expansion in extracellular fluid volume. Salt retention (SR group, n=6) w as induced by physiological saline (0.9% NaCl) 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 t hose 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 prot ocol was used. Basal values of plasma renin activity (PRA) and urinary aldo sterone excretion were determined. Renal functional exploration [clearance (cl.) method] was performed during hypotonic polyuria (induced by oral wate r load) and subsequent moderate antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue). Urinary 6KPGF and TxB(2) concentratio ns were estimated by RIA method and their urinary excretions were determine d at both high and low urinary flow rates. The linear regressions of the ur inary metabolite excretions vs. urinary flow rate were estimated by using t he data obtained in both hypotonic polyuria and antidiuresis. Salt retentio n (SR vs. N group) was effective in decreasing the basal values of plasma r enin activity and urinary aldosterone excretion. Moreover, during hypotonic polyuria it was effective in increasing the absolute and fractional excret ions of sodium and chloride, in the absence of significant variations in me an arterial pressure and creatinine cl. Regarding urinary prostanoid excret ions the following results were obtained. 1. Comparative data for hypotonic polyuria. In the SR vs. N group, the urin ary excretion of 6KPGF was significantly higher, whereas that of TxB(2) was not significantly different. In the SR vs, SD group, the urinary excretion of 6KPGF was not significantly different, whereas that of TxB(2) was signi ficantly lower. 2. Comparative data for the regression lines of the urinary prostanoid excr etions vs. diuresis. In the SR vs. N group, the regression line slope for 6 KPGF excretion was significantly higher, whereas that for TxB(2) excretion was not significantly different. In the SR vs. SD group, the regression lin e slope for 6KPGF excretion was not significantly different, whereas that f or TxB(2) excretion was significantly lower. 3. Correlative data in the SR group during hypotonic polyuria. The plasma c hloride concentration was positively correlated with urinary flow rate, abs olute and fractional chloride excretions, and 6KPGF excretion but not with TxB(2) excretion. In conclusion, functionally effective salt retention in healthy women induc es a selective stimulation of renal synthesis of prostacyclin, unlike salt depletion, in which the synthesis of both PGl(2) and TxA(2) is upregulated. (C) 2000 Harcourt Publishers Ltd.