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Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors

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Chlopicki S., Kozlovski V. I., Gryglewski R. J.

Journal of Physiology and Pharmacology

2003

tom 54

nr 4

Functional role of endothelial alpha2-adrenoceptor in coronary circulation remains unclear. Clonidine, an agonist of alpha2-adrenoceptors, was reported to induce coronary vasodilatation via stimulation of endothelial alpha2-adrenoceptors or coronary vasoconstriction involving vascular smooth muscle alpha2-adrenoceptors. Moreover, H2 receptor-dependent responses to clonidine were described. Here, we reassess the contribution of endothelial alpha2-adrenoceptor and H2 receptors to coronary flow and contractility responses induced by clonidine in the isolated guinea pig heart. We found that clonidine (10-9 - 10-6 M) produced concentration-dependent coronary vasoconstriction without a significant change in contractility. This response was inhibited by the alpha1/alpha2-adrenoceptor antagonist - phentolamine (10-5 M) and the selective alpha2-adrenoceptor antagonist yohimbine (10-6 M), but it was not changed by the selective alpha1-adrenoceptor antagonist prazosin (10-6 M). In the presence of nitric oxide synthase inhibitor, L-NAME (10-4 M) the clonidine-induced vasoconstriction was potentiated. Clonidine at high concentrations of 10-5 – 3 x 10-5 M produced coronary vasodilatation, and an increase in myocardial contractility. These responses were abolished by a selective H2-receptor antagonist, ranitidine (10-5 M), but not by phentolamine (10-5 M). We conclude that in the isolated guinea pig heart, clonidine-induced vasoconstriction is mediated by activation of smooth muscle alpha2-adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by activation of vascular H2 histaminergic receptors. Accordingly, endothelial alpha2-adrenoceptors does not seem to play a major role in coronary flow response induced by clonidine.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Chlopicki S.

1 Gryglewski R. J.

1 Kozlovski V. I.

1 2003

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Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors