In healthy women submitted to a short-term expansion in extracellular fluid volume we have evaluated the urinary excretory profile of the stable metabolites of
prostaglandin(PG) I2 and
thromboxane(TX) A2,
6-keto-PGF1 alpha(6KPGF) and TXB2 respectively, and assessed the physiological role played by the
prostanoids in this experimental condition.
Salt retention (SR group, n=9) was induced by repeated i.v. infusion of
saline solution (
0.9% NaCl). 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 water load) and subsequent moderate antidiuresis (induced by low-dose infusion of an
antidiuretic hormone analogue). Urinary 6KPGF and TXB2 concentrations were estimated by RIA method during
polyuria (P cl. period), early and late antidiuresis (A1 and A2 cl. periods). Paired functional explorations were performed in absence (control study) and presence of
indomethacin. Basal values of plasma
sodium and
potassium concentrations, plasma
renin activity (PRA) and urinary
aldosterone excretion were determined just before the control study. The results in
salt retention were compared to those previously obtained 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 halved dose as in previous studies in
salt depletion the full dose produced prolonged
anuria. (I)
Salt retention vs
salt depletion. The basal values of PRA and urinary
aldosterone excretion were significantly lower. During
polyuria, urinary excretion of 6KPGF, 6KPGF/TXB2 ratio, urinary flow rate,
creatinine cl. and absolute and fractional excretions of
sodium and
chloride were significantly higher. In
salt retention during
polyuria, significant positive correlations were found between 6KPGF excretion and functional excretory parameters. (II)
Indomethacin in
salt retention. The following effects were significant: (a) a reduction in
prostanoid excretions in P and A1 cl. periods only; (b) during
polyuria, an increase in arterial pressure, a reduction in urinary flow rate and
creatinine cl. (saluresis showed not significant reduction). During
polyuria significant positive correlations occurred between the absolute effects of
indomethacin on 6KPGF excretion and those on functional excretory parameters. (III) Comparative effects of
indomethacin in
salt retention and
salt depletion. Despite the double dosage of the
drug, the significant reductions in urinary metabolite excretions were not significantly different during P cl. period and significantly lower in A1 cl. period compared to the corresponding significant reductions in
salt depletion. During
polyuria, the significant increase in arterial pressure was significantly different from the not significant effect in
salt depletion; the not significant effect on saluresis was significantly different from the significant reduction in
salt depletion. The results suggest the following conclusions: (1) The present model showed the functional pattern of the volume-natriuresis; (2) In
salt retention, in contrast with
salt depletion,
indomethacin induced an increase in arterial pressure consistent with the inhibition of a PG-dependent
vasodilator mechanism active at the systemic level; (3) In
salt retention, in contrast with
salt depletion,
indomethacin failed to induce a significant reduction in saluresis. This failure can be attributed to the
drug's blunted effectiveness in inhibiting the renal synthesis of saluretic PGs, and probably to the interference of the concurrent increase in arterial pressure in the renal treatment of
sodium and
chloride.