Effects of histamine in the isolated kitten heart.

The effects of histamine and 4-methylhistamine (4-MH) in isolated kitten heart preparations were examined. Histamine and 4-MH produced dose-dependent increases in the rate of spontaneously beating right atria. The positive chronotropic effect of histamine and 4-MH was unaffected by promethazine but was antagonized by both cimetidine and propranolol. The positive inotropic effects of histamine and 4-MH were studied in the kitten right ventricle strip, right papillary muscle, and left atrium. In all three tissues the positive inotropic effect of histamine and 4-MH was blocked by propranolol and not by either promethazine or cimetidine. In tissues from reserpine-pretreated kittens, histamine caused only a modest increase in rate. The inotropic effects of histamine in the left atrium, right ventricle strip, and right papillary muscle were abolished following reserpine pretreatment. The results of this study indicate two components to the effects of histamine and 4-MH on the kitten heart. The majority of the chronotropic response, and all of the inotropic response, is due to indirect activation of beta adrenoceptors through release of catecholamines. Part of the chronotropic response to both histamine and 4-MH is due to histamine H2-receptor stimulation. Based on the results from reserpine-pretreated animals, it is possible that the release of catecholamines by histamine in the kitten right atrium is through H2-receptor stimulation.