Coronary Vasodilatory, Spasmolytic and cAMP‐Phosphodiesterase Inhibitory Properties of Dihydropyranocoumarins and Dihydrofuranocoumarins

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Abstract
Dihydropyrano- and dihydrofuranocoumarins [23], 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 metabolizing 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 acyloxydihydrofuranocoumarins.