In cold-stressed rats,11 IVa and j and V did not decrease peripheral plasma corticosterone levels at oral doses which exceeded those used to induce a natriuretic response (100 mg/kg).14 However, in rats, V caused adrenal hypertrophy, decreased male sex accessory organ weights, and decreased the rate of gain in body weight. These effects have not been observed with IVa and j.Earlier studies1•'2 had established that VI possessed a highly desirable spectrum of activity in natriuretic and adrenal corticosteroid inhibition assays. It caused marked natriuresis in Na+-depleted rats (a finding conil l) W. A. Zuccarello and G. J. Frishmuth, unpublished observations. sisteut with, but not. proof of, aldosterone inhibition) at oral doses which did not suppress peripheral plasma, corticosterone levels.1 In vitro findings supported the in vivo observations.1/2 Among (lie natriuretic agents tested in our laboratories, VI liad been the most potent of those which appeared to act by selectively inhibiting aldosterone biosynthesis.14 In the present series of compounds, both IVa. and j liad the same desirable biological selectivity as VI but were more active. In comparative studies, it was shown that VI was about two to three times as potent as VII. In turn, IVa. was about• twice as potent as XT, and IVj was about twice as potent as IVa (about four times as potent• as XT, and about eight to twelve times as potent as VII).14 The biological activity of IVj will be described in greater detail elsewhere.
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