Coronary vasodilatory, spasmolytic and cAMP-phosphodiesterase inhibitory properties of dihydropyranocoumarins and dihydrofuranocoumarins.
Twenty-three dihydropyrano- and dihydrofuranocoumarins, most of plant origin, were examined for their effects on the coronary flow of isolated perfused guinea-pig heart, on the Ba2+-induced spasms in isolated guinea-pig ileum, on the cAMP level in guinea-pig heart homogenate and on the cAMP metabolising activity of purified beef heart cAMP-phosphodiesterase. For certain esters of dihydropyranocoumarin- and dihydrofuranocoumarin alcohols coronary vasodilatory and spasmolytic activities comparable to those of papaverine were observed. A very close correlation between the coronary vasodilatory and the spasmolytic activity was found. The most potent structures maximally increased the cAMP level from 19 pmol/mg protein to about 60 pmol/mg protein and inhibited the cAMP-phosphodiesterase activity with about 90%. The potencies were comparable to those of papaverine. A significant correlation was obtained between the coronary vasodilatory and the cAMP-phosphodiesterase inhibitory activity. The results indicate involvement of cAMP-phosphodiesterase inhibition in coronary vasodilatory effects of acyloxydihydropyrano- and acyloxydihydrofurano-coumarins.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics; D014665:Vasodilator Agents
D003374:Coumarins; D010276:Parasympatholytics; D014665:Vasodilator Agents; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases