Relation of rates of excretion of urinary prostaglandin E metabolites to administration of angiotensin, aldosterone, and spironolactone in vivo.

Using a new radioimmunoassay for measurement of the mixed urinary metabolites of prostaglandin E (U-PGE-M) as an indirect measure of the endogenous formation of prostaglandin E, the effect of aldosterone, angiotensin-II, and spironolactone on excretion rates of U-PGE-M in normal and adrenalectomized rat urines was studied. In normal rats, pharmacologically inactive doses of aldosterone and angiotensin-II stimulated, while pharmacologically inactive doses of spironolactone inhibited U-PGE-M excretion in a linear, log-dose manner. Pharmacologically inactive doses of spironolactone inhibited aldosterone and angiotensin-II-stimulated U-PGE-M excretion, in a linear, log-dose relation. Adrenalectomy resulted in elevation of normal rat basal U-PGE-M excretion rate. Angiotensin-II further stimulated, and spironolactone depressed the elevated U-PGE-M levels of adrenalectomized rats. Spironolactone inhibited angiotensin-II-stimulated increase of U-PGE-M in adrenalectomized rats, the first unequivocal demonstration of inhibition of an effect of angiotensin-II by spironolactone. The results demonstrate a strong mechanistic relationship of aldosterone, angiotensin-II, spironolactone, to prostaglandin E (PGE), and demonstrate possible new pathways for regulating blood pressure via changes in phospholipase/prostaglandin synthetase activity.