Further evidence of interaction between vasodilator β2- and vasoconstrictor α2-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats

Document Type

Journal Article

Publication Date

1-1-1989

Journal

Journal of Cardiovascular Pharmacology

Volume

14

Issue

6

DOI

10.1097/00005344-198912000-00013

Keywords

Clenbuterol; Epinephrine; Pentobarbital; Urethane; α -Adrenoceptor 2; β -Adrenoceptor 2

Abstract

The importance of the interaction of α- and β-adrenoceptors in maintaining vascular tone in rats was studied. This interaction after clenbuterol (CLEN) treatment indicates an important contribution of the circulating epinephrine (EPI) levels. In urethane-anesthetized rats, the β2-adrenoceptor antagonist (CI 118.551 was more effective in antagonizing isoproterenol-induced hypotension (mainly β2-mediated) than tachycardia (mainly β1-mediated). Intravenous (i.v.) administration of the α2-adrenoceptor agonist clonidine (CLO) induced an initial pressor response followed by a more prolonged hypotension and bradycardia. The initial hypertensive effect was potentiated by previous acute administration of ICI 118.551 as well as by the nonselective β-adrenoceptor antagonist propranolol, but not by metoprolol, a more selective β1-blocker. Fourteen days of administration of the β2-adrenoceptor agonist CLEN [0.3 mg/kg, subcutaneously (s.c.) twice daily], a treatment that induces desensitization of β2-mediated vasodilation, increased the pressor response induced by CLO, an effect that was not observed in pentobarbital-anesthetized rats. In any case, neither β-blockers nor CLEN treatment affects the hypotension and bradycardia induced by CLO. Mean blood pressure (BP) of CLEN-treated rats was increased under urethane anesthesia but not under pentobarbital anesthesia. Catecholamine levels (principally EPI) were higher in urethane-anesthetized rats. These results provide further evidence of a functional interaction between α2- and β2-adrenoceptor-mediated responses in rat vasculature and suggest that vasodilator β2-adrenoceptors might contribute to the determination of peripheral vascular tone when circulating EPI is substantially elevated.

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