Spironolactone decreases the formation of prostaglandins and related substances from arachidonic acid in rat vascular rings and human platelets.
10(-6) and 10(-5) M spironolactone decreased the total conversion of 14C-arachidonic acid to 6-keto-prostaglandin (PG) F1 alpha, PGE2 and PGF2 alpha in rat aortic and mesenteric artery rings by 29 and 55% respectively. Same concentrations of spironolactone decreased the total conversion of 14C-arachidonic acid to thromboxane (TX) B2, PGE2 and PGF2 alpha in human platelets by 3 and 21% respectively. These findings provide a possible basis for the significant inhibition by spironolactone of vascular reactivity to norepinephrine. Spironolactone seemed to act in both vascular tissue and platelets to suppress PG synthesis at the prostaglandin endoperoxide synthetase level. This direct action of spironolactone could contribute to its vascular and other effects.
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D001158:Arteries / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D013148:Spironolactone / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013148:Spironolactone; D013929:Thromboxane B2