Role of Renal Prostaglandins and Relationship to Renin, Aldosterone, and Antidiuretic Hormone during Salt Depletion in Man*

Effect of Exogenous Prostaglandin E₂ on Plasma Antidiuretic Hormone in Normal Man

“…This hypothesis would unify the above-reported findings [7,8] with some of our recent results. In our studies, in fact, endogenous PGE2 and 6-keto-PGF|a were stimulated, instead of being in hibited, with non-pressor and low-pressor doses of an giotensin II and with captopril, and we did not observe an effect of these prostaglandins on the synthesis of ADH, whilst it was evident that angiotensin II, and not prostaglandin, is an important non-osmotic stimulus for ADH [9,10].…”

“…In normal volunteers the inhibition of prostaglandin synthesis with indomethacin lowered the urinary excre tion of ADH, supporting a role of endogenous prosta glandins in the synthesis of vasopressin [7,8] even if this suppression of ADH might have resulted indirectly from increased water retention [8], But PGE2 enhances PRA and angiotensin synthesis [15][16][17] and indomethacin impairs directly or indirectly the renin-angiotensin sys tem in vivo both under basal conditions and when renin is stimulated by haemorrhage [16,18,19], so that it is possible that the reported effect of endogenous prosta glandins on ADH [7,8] might be related to modifica tions of the renin-angiotensin system rather than, or in adition to, prostaglandins per se. This hypothesis would unify the above-reported findings [7,8] with some of our recent results.…”

“…Studies in vitro, animals and humans have demon strated that vasopressin and DDAVP increase renal syn thesis and excretion of prostaglandins [4][5][6], and there is evidence that prostaglandins, in turn, increase the syn thesis of ADH [7,8,[11][12][13].…”

“…Stud ies performed in man, in fact, have given conflicting results. In man, inhibition of prostaglandin synthesis with indomethacin lowered the urinary excretion (and thus the production) of ADH, suggesting a role of endog enous prostaglandins on the release of ADH [7,8]. In contrast, we did not observe an effect of endogenous PGE2 and of 6-keto-PGFic on plasma ADH in normal volunteers in whom these prostaglandins were stimu lated with angiotensin II [9] and captopril [10], Thus, while the role of endogenous PGE2 on the release of ADH is still unclear, it has been shown that high doses of exogenous vasodilator prostaglandins enhance the re lease of ADH in vitro [11,12] and in animals [13], but we do not know of studies in humans employing exoge nous PGE2 in order to evaluate their ability to increase plasma levels of ADH.…”

Nonsteroidal Anti-Inflammatory Drugs and Antihypertensives

“…The reduction of the natriuretic efficiency of loop diuretics is likely the result of interference at several sites crucial to diuretic action. The reduction of the glomerular filtration rate that is sometimes observed with NSAIDs [18] is a likely, but not a major factor in the observed reduction, except in states of renal underperfusion such as congestive heart failure, volume depletion, and liver cirrhosis. NSAIDs alter the access of diuretics to their tubular site of action by competing for transport at the organic acid secretory pathway of the proximal tubule [16].…”