Abstract
MJ 8592-1, an orally active diuretic indolylindoline derivative, effectively reversed the relative oliguria induced by ADH (Pitressin®) in ethanol-saline primed intact rats. It was 5.5, .96 and >18 times as potent, respectively, as furosemide, HCTZ and triamterene in producing a 100% increase in Na excretion in the presence of ADH. Since MJ 8592-1 also elicited a diuretic-saluretic response in ethanolsaline primed rats in the absence of ADH, the antagonism to exogenous vasopressin may be classified as non-specific. In adrenalectomized rats, MJ 8592-1, like triamterene, produced dose-related electrolyte excretion responses in both the presence and absence of exogenous DOCA. Thus, while MJ 8592-1 was effective in counteracting mineralocorticoid-induced Na retention in the distal tubule, it was also capable of increasing Na excretion by a mechanism independent of any direct interactions with adrenal cortical steroids or tubular sites influenced by these hormones.
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