RELATIONSHIP BETWEEN RENAL PROSTAGLANDIN-E AND RENAL SODIUM HANDLING DURING WATER IMMERSION IN NORMAL MAN

Previous studies from this laboratory have demonstrated that the central hypervolemia induced by water immersion to the neck (NI) constitutes a suitable model for assessing the hormonal response to volume expansion without concomitant alterations in plasma composition. The NI model was used to assess in a kinetic fashion the relationship between renal prostaglandin E (PGE) and renal sodium handling. Nine normal subjects were studied twice in the sodium-replete state during NI: with indomethacin (Ind) pretreatment (50 mg q6h x 5)(NI + Ind) and without indomethacin (NI). Urinary sodium, potassium, and PGE excretion (UpgeV) were measured hourly. NI was associated with marked increases in UNaV [from 87 ± 20 (SE) to 219 ± 25 μEq/min (P<0.05)] and UpgeV [from 6.4 ± 1.4 to 12.9 ± 2.5 ng/min (P<0.05)]. Although indomethacin administration lowered the basal rate of UpgeV prior to immersion, it neither prevented the subsequent augmentation of UpgeV during NI + Ind nor affected the magnitude of the natriuresis during NI + Ind. Subsequently, six of the subjects were restudied following dietary sodium restriction (10 mEq/day). The changes in UpgeV during NI and NI + Ind were qualitatively similar to those observed in the sodium-replete state. In contrast to the sodium-replete studies, however, the natriuresis of immersion was attenuated markedly by indomethacin pretreatment. In summary, the data demonstrate that immersion-induced central volume expansion is associated with a striking increase in renal PGE excretion which is attenuated but not prevented by indomethacin. In addition, indomethacin administration attenuates markedly the natriuretic response of immersion in sodium-depleted, but not in sodium-replete, normal subjects. These observations are consistent with the suggestion that renal PGE may constitute a determinant of the renal response to volume expansion in sodium-depleted man.