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.
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006973:Hypertension / Q000209:etiology; D008297:Male; D011458:Prostaglandins E / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology*
D011458:Prostaglandins E; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone