Evidence for an in vivo antagonism between vasopressin and prostaglandin in the mammalian kidney

Abstract

These studies were undertaken to examine whether an antagonism between vasopressin and prostaglandin occurs in vivo in the mammalian kidney. All experiments were performed in steroid replaced hypophysectomized dogs undergoing a water diuresis. In the first group of studies the effect of two consecutive intravenous doses (100 mU) of vasopressin was examined. The second dose of vasopressin was preceded by an injection of the carrier solution for solubilizing indomethacin or meclofenamate. No enhancement of the antidiuretic effect of the second dose of vasopressin was observed as urinary osmolality (Uosm) increased from 92±5 to 252±18 mosmol/kg H2O (P < 0.001) after the first dose and from 109±8 to 209±10 mosmol/kg H2O (P < 0.001) after the second dose of vasopressin. In another group of studies the second dose of vasopressin was preceded by the administration of a potent inhibitor of prostaglandin synthesis, indomethacin (2 mg/kg). The Uosm increased from 93±9 to 244±33 mosmol/kg H2O (P < 0.001) after the first dose of vasopressin, but after the second dose of vasopressin the Uosm increased to a significantly greater degree from 106±14 to 702±69 mosmol/kg H2O (P < 0.001). In a third group of studies the antidiuretic effect of the same 100 mU dose of vasopressin was examined before and after the administration of meclofenamate (2 mg/kg), an inhibitor of prostaglandin synthesis which is chemically dissimilar from indomethacin. Uosm increased from 83±7 to 216±16 mosmol/kg H2O (P < 0.001) after the first dose and from 101±8 to 734±86 mosmol/kg H2O (P < 0.001) after the second dose of vasopressin. As in the indomethacin studies this enhancement of the antidiuretic effect of vasopressin after inhibition of prostaglandin synthesis was highly significant (P < 0.001). These results therefore implicate a physiological role of prostaglandin in modulating the hydroosmotic effect of vasopressin in the mammalian kidney.