Role of prostaglandins in the regulation of renal water excretion

Abstract

Accumulating evidence suggests that the renal prostaglandin (PG) system participates in the regulation of renal water excretion. In the renal medulla, high PG synthetase activity is present in the interstitial cells [1] and the collecting duct epithelium [2, 3]. Also, in vitro studies in the toad urinary bladder [4] and the isolated collecting duct [5] have demonstrated that PGE suppresses vasopressin-induced changes in water permeability in these tissues, possibly by inhibiting vasopressin-activated adenylcyclase. In addition, administration of vasopressin to acutely hypophysectomized dogs [6] or healthy volunteers [7] resulted in a significantly enhanced urinary concentrating response when PG synthesis was inhibited with nonsteroidal antiinflammatory agents. Furthermore, in vitro studies in rabbit renomedullary interstitial cell cultures [8] and the toad urinary bladder [9] have shown that arginine vasopressin stimulates PGE2 biosynthesis in these tissues. Therefore, a short loop feedback system has been proposed in which arginine vasopressin itself stimulates its antagonist PGE2 in collecting duct epithelial cells [9, 101. The mechanism of the antagonistic action of PGE on vasopressin-induced changes in water excretion is still controversial. In addition to the above mentioned in vitro studies, the concept of an inhibitory action of PGE on vasopressin-activated adenylcyclase has also been supported by measurements of renal medullary tissue cyclic adenosine monophosphate (cyclic AMP) concentrations in response to exogenous vasopressin in the rat, which significantly increased following inhibition of PG synthesis with indomethacin [11]. The concentrating ability of the kidney is mainly dependent on: (1) glomerular filtration rate (GFR) and proximal tubular function to determine fluid and solute delivered to distal segments of the nephron, (2) sodium and chloride absorption in the thick