Stereospecific stimulation of coronary vascular PGI2 by organic nitrates--studies with the new compound teopranitol (KC-046).
PGI2 release of bovine coronary arteries (BCA) was studied in vitro (bioassay) under control conditions and in presence of the new isoidide-nitrate teopranitol (2-(gamma-theophylline-7-ylpropylamino)-2-desoxy-L-isoidide- 5-nitrate- bifumarate) (KC-046). Teopranitol dose-dependently stimulated (2-200 nmoles/1) PGI2 release 2-3-fold. This action was inhibited by both methylene blue (150 mumoles/1) and indomethacin (11 mumoles/1). The 5-[endo] stereoisomere (KC-144) was inactive, although both compounds produced an equally potent relaxation of isolated BCA strips. Similar stereospecificity was found for isosorbide nitrates. It is suggested that stimulation of coronary vascular PGI2 by organic nitrates is critically determined by the steric position of the free nitrate group(s), whereas the vasodilation is a more general property.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009566:Nitrates / Q000494:pharmacology; D013402:Sugar Alcohols / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology
D009566:Nitrates; D013402:Sugar Alcohols; D002110:Caffeine; C042286:teopranitol; D013806:Theophylline; D011464:Epoprostenol