Renal prostanoids: physiological relevance in healthy salt-depleted women

The effective role played by prostanoids in the control of renal function h as been investigated in healthy women with salt depletion. Salt depletion ( SD2 group, n = 6) was induced by low sodium chloride dietary intake (less t han or equal to 60 mmol per day) and combined treatment with natriuretic an d potassium-sparing drugs. At the end of the depletive treatment, the cumul ative sodium deficit was 513 +/- 56 mmol. The renal function and urinary ex cretions of prostaglandin (PG) E-2, 6-keto-PGF(1 alpha) (6KPGF) and thrombo xane (Tx) B-2 were evaluated during hypotonic polyuria. The basal values of plasma sodium and potassium concentrations, plasma renin activity (PRA) an d urinary aldosterone excretion were determined before the induction of hyp otonic polyuria. Paired studies were performed in the absence (control) and presence of indomethacin both in the SD2 group and in a previously studied group (N2, n = 6) of healthy women in normal sodium and potassium balance. Women in normal balance received 100 mg i.m, of indomethacin, salt-deplete d women received only 50 mg (because 100 mg of the drug produced a prolonge d anuria). In the SD2 vs. N2 group in the absence of treatment the followin g significant differences were found: (a) higher basal values of PRA and ur inary aldosterone excretion; CD) higher urinary excretions of 6KPGF and TxB (2) but not of PGE(2); (c) lower values of urinary flow rate, creatinine cl earance, absolute and fractional excretions of sodium and chloride, plasma osmolality and plasma electrolyte concentrations. The effects of the indome thacin have been assessed as percentage variations by using paired data for each experimental group. In the SD2 vs. N2 group the reduction in urinary excretions of 6KPGF, TxB(2) and potassium as well as in creatinine clearanc e were not significantly different. On the other hand, the following were s ignificantly different: (a) the lower reduction in PGE2 excretion; (b) the higher reduction in urinary flow rate and in C-H2O; (c) the reductions in a bsolute and fractional excretions of sodium and chloride, and the increase in plasma potassium concentration, significant in the SD2 group but not in the N2 group. The data suggest that: (1) when stimulated by salt depletion the renal biosynthetic pathways of PGI(2) and TxA(2) showed greater sensiti vity to indomethacin inhibition; (2) the effects of the neurohormonal syste ms activated by salt depletion were either modulated or mediated by renal p rostanoids.