Inotropic and chronotropic effects of vasodilators

Although vasodilators are used with increasing frequency for the treatment of heart failure and myocardial ischemia, their direct effects on cardiac muscle have not been completely characterized. To delineate the action of vasodilators on mammalian myocardium, the chronotropic and inotropic effects of vasodilators on isolated guinea-pig atria (n = 163) have been determined. The spontaneous frequency and the peak rate of isometric force development at a fixed frequency of 200/min were used as indexes of chronotropy and inotropy. The potency series for negative chronotropy was diltiazem > D600 > verapamil > lidoflazine > bepridil > prenylamine > perhexiline > nifedipine. The potency series for negative inotropy differed substantially, exhibiting the sequency nifedipine > D600 > verapamil > bepridil > lidoflazine > prenylamine > perhexiline > diltiazem. Therefore, nifedipine acted as an 'inoselective' and diltiazem as a 'chrono-selective' depressant. Other vasodilators, including papaverine, nitroglycerin, nitroprusside, adenosine, dipyridamole, diazoxide and hydralazine exerted no or negligible negative chronotropic or inotropic effects even at high concentration (10^-5 M). Therefore, only vasodilators classified among the calcium antagonists proved to have appreciable direct myocardial effects. This supports the view that these drugs constitute a category of agents distinct from classical vasodilators.