Prostaglandin synthesis inhibition and the action of vasopressin: studies in man and rat

Abstract

Prostaglandin (PG) synthetase inhibitors were employed to define the in vivo role of PG''s in renal water excretion. In 7 healthy volunteers, indomethacin administration was associated with a significant increase in minimal urinary osmolality (Uosmol) (P < .02) and a decrease in maximal free water clearance (CH2O) (P < .05) after a water load, as well as with a greater increase in Uosmol (P < .025) and a decrease in CH2O (P < .005) following the i.v. injection of 40 mU of vasopressin. In awake, water diuresing rats 250 mU of s.c. antidiuretic hormone in oil increased Uosmol from 108 .+-. 10 to 313 .+-. 36 mosmol/kg in rats receiving a blank, from 110 .+-. 11 to 457 .+-. 33 mosmol/kg in 15 rats receiving aspirin and from 113 .+-. 16 to 581 .+-. 47 mosomol/kg in 14 rats on indomethacin. Neither drug itself affected water excretion differently from concurrently studied controls on the blank. Doses of indomethacin and aspirin were equiinhibitory (85-90%) of PGE2 biosynthesis. Indomethacin but not aspirin consistently decreased the activity of cyclic AMP phosphodiesterase in the papilla (P < .01). In the unanesthetized animal inhibition of PG synthesis potentiates the action of antidiuretic hormone by an intrarenal mechanism independent of changes in renal hemodynamics and cation excretion. This mechanism is probably mediated by a direct alteration in the water permeability of the collecting duct epithelium. The observed enhancement of the antidiuretic action of antidiuretic hormone may be further potentiated but is not dependent on the inhibition of phosphodiesterase activity.