Effect of Inhibition of Prostaglandin Synthesis on the Natriuresis Induced by Saline Infusion in Man

Abstract

1. The effect of oral administration of an inhibitor of prostaglandin synthetase, indomethacin, on the natriuresis induced by the infusion of sodium chloride (saline) was studied in 11 healthy volunteers. 2. The administration of indomethacin did not alter sodium excretion before saline infusion, but it resulted in a significant increase of the natriuresis after saline infusion. This increase was not accompanied by any change in post-infusion urine flow rate or free water reabsorption. 3. It is suggested that intrarenal prostaglandins might suppress the natriuretic effect of saline infusion, probably by increasing sodium reabsorption in the distal nephron.

Relationship between renal prostaglandin E and renal sodium handling during water immersion in normal man.

“…Attempts to define the effect of prostaglandin release on the natriuresis of ECVE by inhibition of prostaglandin synthesis have been contradictory, with reports suggesting that inhibition of prostaglandin synthesis may be either antinatriuretic (Verberckmoes et al, 1976;Donker et al, 1976;Patak et al, 1975;Berg, 1977;Diising et aL, 1976), natriuretic (Kirschenbaum and Stein, 1977;Mountokalakis et al, 1978;Kirschenbaum and Stein, 1976), or fail to affect renal sodium handling (Bohan and Wesson, 1976;Bailie et al, 1976). In several studies, inferences regarding the role of indomethacin on renal sodium excretion were drawn by assessing the natriuretic response to furosemide before and after indomethacin administration (Patak et al, 1975;Bailie et al, 1976).…”

“…Papanicolaou et al (1975) assessed renal venous PGE levels without determining renal sodium excretion simultaneously. Although Mountokalakis et aL (1978) demonstrated that indomethacin administration augmented the natriuretic response to saline administration, renal PGE was not determined. Furthermore, in both studies, acute ECVE was induced by the administration of an intravenous saline load which presumably altered plasma composition.…”

“…In several studies, inferences regarding the role of indomethacin on renal sodium excretion were drawn by assessing the natriuretic response to furosemide before and after indomethacin administration (Patak et al, 1975;Bailie et al, 1976). Additional studies have assessed renal sodium excretion during steady state conditions before and after the administration of either indomethacin (Verberckmoes et al, 1976;Donker et al, 1976;Mountokalakis et aL, 1978) or acetylsalicylic acid (Berg, 1977;Bowden et aL, 1978).…”

“…Only two studies to date have assessed the effect of acute ECVE in man (Mountokalakis et al, 1978;Papanicolaou et al, 1975). Papanicolaou et al (1975) assessed renal venous PGE levels without determining renal sodium excretion simultaneously.…”

“…Circ Res 45: 71-80, 1979 DESPITE extensive study, the relationship of the renal synthesis of prostaglandins to renal sodium excretion remains controversial (Dunn and Hood, 1977). Although it has been proposed that alterations in prostaglandin release may constitute a determinant of the natriuretic response to extracellular fluid volume expansion (ECVE) (Gross and Bartter, 1973; Verberckmoes et al, 1976; Donker et al., 1976;Patak et al, 1975; Berg, 1977; Diising et al., 1976), the effect of volume expansion on endogenous prostaglandin release and the contribution of endogenous renal prostaglandins to the natriuresis of volume expansion remain unsettled (Kirschenbaum and Stein, 1977;Mountokalakis et al, 1978; Bohan and Wesson, 1976). The contradictory nature of the available data may relate in part to species differences and to attempts to extrapolate from studies in anesthetized or acutely operated animals to man.…”