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  • Title: Interaction of alpha-adrenergic imidazolines with cardiac histamine H2-receptors.
    Author: Zavecz JH, Yellin TO.
    Journal: Eur J Pharmacol; 1981 May 08; 71(2-3):297-306. PubMed ID: 6166486.
    Abstract:
    We have investigated in the isolated, perfused guinea pig heart whether a alpha-adrenergic imidazolines, tolazoline and tetrahydrozoline stimulate histamine H2-receptors directly or via the release of endogenous histamine. At 30 degrees C neither tolazoline nor tetrahydrozoline released histamine. However, both increased heart rate, contractility, and decreased coronary vascular resistance as a function of dose. The H2-receptor antagonists cimetidine and tiotidine blocked the effects of tolazoline and tetrahydrozoline. The actions of tetrahydrozoline were confined to its 1-isomer. At 37 degrees 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 degrees C. All other responses to the two drugs were the same at 30 and 37 degrees C. Our results suggest that tolazoline and tetrahydrozoline directly stimulate histamine H2-receptors. Because of the differences in the structures of imidazolines and histamine, these findings have implications for the current hypothesis regarding histamine H2-receptor activation.
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