POTENTIATION OF THE EFFECTS OF SODIUM-NITROPRUSSIDE AND OF ISOPROTERENOL BY SELECTIVE PHOSPHODIESTERASE INHIBITORS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 23  (2) , 424-430
Abstract
A series of alkylated xanthines [1-methyl-3-isobutylxanthine, 1-methyl-3-isobutyl-8-methoxymethylxanthine and 1-isoamyl-3-isobutylxanthine] and a papaverine analog [6-isopropoxy analog] with a range of potencies and selectivities as inhibitors of phosphodiesterases isolated from bovine coronary arteries were identified. The abilities of these inhibitors to potentiate the relaxant effects of sodium nitroprusside (SNP) and isoproterenol were predictable from the potencies to inhibit the calmodulin-sensitive and the cAMP-specific forms of phosphodiesterase, respectively. Although the xanthines potentiated the SNP- and isoproterenol-induced increases in cGMP and cAMP, respectively, in manners that were consistent with the involvement of the respective cyclic nucleotides in the relaxation process, the papaverine analog did not potentiate isoproterenol-induced increases in cAMP levels. Increases in cGMP levels are apparently responsible for the relaxation of coronary artery strips by SNP. The calmodulin-sensitive phosphodiesterase activity evidently does not contribute significantly to the hydrolysis of cAMP in the intact bovine coronary artery smooth muscle cells.