Cellular calcium uptake in the action of prostaglandins on renal water excretion

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 (U Osm ) achieved in the contralateral control kidney was 338 ± 40 mOsm/kg H 2 O but was only 270 ± 23 mOsm/kg H 2 O 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 U Osm increased to a mean of 650 ± 103 mOsm/kg H 2 O but only to 280 ± 22 mOsm/kg H 2 O 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 U Osm rose to 590 ± 78 mOsm/kg H 2 O in the control kidney but only to 278 ± 11 mOsm/kg H 2 O 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. La captation cellulaire de calcium dans l'action des prostaglandines sur l'excretion renale d'eau. Le role de la captation cellulaire de potassium sur la reponse antidiuretique a la vasopressine a ete etudiee chez les chiens anesthesies et soumis a une diurese aqueuse. Une perfusion intrarenale de verapamil determine une attenuation discrete de la reponse a d'hormone antidiuretique (ADH) puisque l'osmolalite urinaire (U Osm ) obtenue dans le rein controlateral est de 338 ± 40 mOsm/kg H 2 O mais seulement de 270 ± 23 mOsm/kg H 2 O (P Osm des reins controles a augmente jusqu'a une valeur de 650 ± 103 mOsm/kg H 2 O, mais seulement a 280 ± 22 mOsm/kg H 2 O du cote perfuse. Ainsi le verapamil abolit l'effet de l'inhibition de PG. De la meme facon, chez cinq chiens, un autre inhibiteur du transport du calcium chimiquement different, le proadifen (0,375 mg/kg/min), abolit aussi l'effet des inhibiteurs de PG puisque U Osm augmente a 590 ± 78 mOsm/kg H 2 O dans les reins controles, mais seulement a 278 ± 11 mOsm/kg H 2 O dans les reins perfuses avec le proadifen. Ni la vasodilatation prealable, ni l'augmentation de l'excretion de substances dissoutes par le mannitol a un niveau comparable a celui observe avec le verapamil ne reproduisent l'effet des inhibiteurs de la captation de calcium. Les resultats obtenus in vivo demontrent donc que l'effet des inhibiteurs de PG, l'augmentation de l'effet hydroosmotique de la vasopressine, implique le transport cellulaire du calcium.