Interaction of α-adrenergic imidazolines with cardiac histamine H 2-receptors

Abstract

We have investigated in the isolated, perfused guinea pig heart whether the α-adrenergic imidazolines, tolazoline and tetrahydrozoline stimulate histamine H 2-receptors directly or via the release of endogenous histamine. At 30°C neither tolazoline nor tetrahydrozoline released histamine. However, both increased heart rate, contractility, and decreased coronary vascular resistance as a function of dose. The H 2-receptor antagonists cimetidine and tiotidine blocked the effects of tolazoline and tetrahydrozoline. The actions of tetrahydrozoline were confined to its l-isomer. At 37°C tolazoline, but not tetrahydrozoline, released histamine into the coronary perfusate. The maximum tolazoline-induced change in heart rate was 2.5–3.0 times greater than tetrahydrozoline's, in distinct contrast to their identical effect at 30°C. All other responses to the two drugs were the same at 30 and 37°C. Our results suggest that tolazoline and tetrahydrozoline directly stimulate histamine H 2-receptors. Because of the differences in the structures of imidazolines and histamine, these findings have implications for the current hypothesis regarding histamine H 2-receptor activation.