Cellular calcium uptake in the action of prostaglandins on renal water excretion.
The role of cellular calcium uptake in the antidiuretic response to vasopressin was studied in anesthetized dogs undergoing water diuresis. In prostaglandin (PG) intact animals, an intrarenal infusion of verapamil caused only a modest blunting of the response to antidiuretic hormone (ADH), because the urinary osmolality (UOsm) achieved in the contralateral control kidney was 338 +/- 40 mOsm/kg H2O but was only 270 +/- 23 mOsm/kg H2O in the verapamil-infused kidney. The possibility was then studied that PG inhibit the action of ADH by impairing cellular calcium uptake. If so, verapamil would be expected to abolish the effect of PG inhibition to enhance the action of ADH. In eight PG-inhibited dogs, the control kidney's UOsm increased to a mean of 650 +/- 103 mOsm/kg H2O but only to 280 +/- 22 mOsm/kg H2O in the infused side. Thus, verapamil abolished the effect of PG inhibition to enhance the action of ADH. Likewise in five dogs a second chemically dissimilar inhibitor of calcium transport, proadifen, also abolished the effect of PG inhibitors as UOsm rose to 590 +/- 78 mOsm/kg H2O in the control kidney but only to 278 +/- 11 mOsm/kg H2O in the proadifen-infused kidney. Neither prior vasodilatation nor an increased solute excretion with mannitol of a degree observed with verapamil mimicked the effect of the calcium uptake blockers to inhibit the action of ADH. The present in vivo studies therefore demonstrate that the effect of PG inhibitors to enhance the hydroosmotic effect of vasopressin involve cellular calcium transport.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011335:Proadifen / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D011453:Prostaglandins; D014667:Vasopressins; D011335:Proadifen; D014700:Verapamil; D002118:Calcium; D007213:Indomethacin