Volume induced natriuresis in healthy women: renal metabolism of prostacyclin and thromboxane, and physiological role of prostanoids

In healthy women submitted to a short-term expansion in extracellular fluid Volume we have evaluated the urinary excretory profile of the stable metab olites of prostaglandin(PG) I-2 and thromboxane(TX) A(2), 6-keto-PGF(1 alph a) (6KPGF) and TXB2 respectively, and assessed the physiological role playe d by the prostanoids in this experimental condition. Salt retention (SR gro up, n=9) was induced by repeated i.v. infusion of saline solution (0.9% NaC l). At the end of the treatment the body weight had increased by 0.7 +/- 0. 2 kg (mean +/- SEM) (P < 0.05). Renal functional exploration [clearance (cl .) method] was performed during hypotonic polyuria (induced by oral wafer l oad) and subsequent moderate antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue). Urinary 6KPGF and TXB2 concentrations we re estimated by RIA method during polyuria (P cl. period), early and late a ntidiuresis (A1 and A2 cl. periods). Paired functional explorations were pe rformed in absence (control study) and presence of indomethacin. Basal valu es of plasma sodium and potassium concentrations, plasma renin activity (PR A) and urinary aldosterone excretion were determined just before the contro l study. The results in salt retention were compared to those previously ob tained in healthy women submitted to a moderate salt depletion (SD2 group, n=6), in absence and presence of the drug. Women in salt retention received 100 mg i.m. of the drug, whereas salt-depleted women received only a halve d dose as in previous studies in salt depletion the full dose produced prol onged anuria. (I) Salt retention vs salt depletion. The basal values of PRA and urinary aldosterone excretion were significantly lower. Du ri ng polyu ria, urinary excretion of 6KPGF, 6KPGF/TXB2 ratio, urinary flow rate, creat inine cl. and absolute and fractional excretions of sodium and chloride wer e significantly higher. In salt retention during polyuria, significant posi tive correlations were found between 6KPGF excretion and functional excreto ry parameters, (II) Indomethacin in salt retention. The following effects w ere significant: (a) a reduction in prostanoid excretions in P and A1 cl. p eriods only; (b) during polyuria, an increase in arterial pressure, a reduc tion in urinary flow rate and creatinine cl. (saluresis showed not signific ant reduction). During polyuria significant positive correlations occurred between the absolute effects of indomethacin on 6KPGF excretion and those o n functional excretory parameters. (III) Comparative effects of indomethaci n in salt retention and salt depletion. Despite the double dosage of the dr ug, the significant reductions in urinary metabolite excretions were not si gnificantly different during P cl. period and significantly lower in A1 cl. period compared to the corresponding significant reductions in salt deplet ion. During polyuria, the significant increase in arterial pressure was sig nificantly different from the not significant effect in salt depletion; the not significant effect on saluresis was significantly different from the s ignificant reduction in salt depletion. The results suggest the following c onclusions: (1) The present model showed the functional pattern of the volu me-natriuresis; (2) In salt retention, in contrast with salt depletion, ind omethacin induced an increase in arterial pressure consistent with the inhi bition of a PG-dependent vasodilator mechanism active at the systemic level ; (3) In salt retention, in contrast with salt depletion, indomethacin fail ed to induce a significant reduction in saluresis. This failure can be attributed to the drug's blunted effectiveness in inhib iting the renal synthesis of saluretic PGs, and probably to the interferenc e of the concurrent increase in arterial pressure in the renal treatment of sodium and chloride. (C) 2001 Harcourt Publishers Ltd.