Role of prostaglandins in the regulation of renal water excretion

Abstract

To external previous in vitro studies, we have shown in healthy human subjects and in patients with central diabetes insipidus that vasopressin is a much weaker stimulus of renal PGE synthesis than is AII. Therefore, vasopressin-dependent renal PG synthesis may become evident only under conditions of low activity of the renin-angiotensin system. Patients with central diabetes insipidus were found to have a low renal PG synthesis as reflected by a decreased urinary PGE2 excretion that was independent of urinary flow rate. The tubular effects of endogenous arginine vasopressin, as well as its analogues lysine-vasopressin and desaminosarginine vasopressin, are markedly enhanced following the inhibition of PG synthesis. This probably results from: (1) increased sodium and chloride absorption in the thick ascending limb of Henle's loop, (2) increased systolic cyclic AMP formation in collecting duct epithelial cells, and (3) decreased medullary blood flow with reduced washout of solute from the medullary interstitium. In addition, systemic inhibition of PG synthesis was found to also indirectly or directly supress osmoreceptor-mediated stimulation of central vasopressin secretion. Arginine vasopressin, as well as its analogues lysine vasopressin and desamino-arginine vasopressin, potentially stimulates renal synthesis of PGE. Medullary interstitital osmolality also may enhance PGE synthesis. Intrarenal PG may inhibit vasopressin-activated adenylcyclase activity in collecting duct epithelial cells, thus attenuating vasopressin-dependent transtubular water movement. PG may also inhibit sodium and chloride absorption in the thick ascending limb of Henle's loop and increase medullary blood flow, thus lowering medullary interstitial osmotic driving forces. Therefore, a PG-dependent, complex, intrarenal short-loop feedback, as well as possible extrarenal mechanisms, may be involved in the renal regulation of water balance.