Interaction between beta 2- and alpha 2-adrenoceptor responses in the vascular system: effect of clenbuterol

Subchronic treatment with the beta 2-adrenoceptor agonist, clenbuterol (0.3 mg X kg-1, twice daily for 14 days), significantly increased the median blood pressure in anaesthetized normotensive rats. The treatment produced a marked reduction in the vasodilator effect of isoproterenol. Acute clenbuterol administration (0.01 mg X kg-1 i.v.) reduced the contractile response induced by the alpha 2-adrenoceptor agonists, guanabenz or B-HT 920, and the alpha 1- and alpha 2-adrenoceptor agonist, clonidine, whereas it did not affect the vasoconstriction by the alpha 1-adrenoceptor agonist, methoxamine, in the pithed rat. Subchronic treatment with clenbuterol attenuated the effect of the beta 2-adrenoceptor agonist on the vascular alpha 2-adrenoceptor responses and enhanced the alpha 1-adrenoceptor response to phenylephrine in pithed rats. The effect of the beta 2-adrenoceptor agonist was reduced by 1- but not d-propranolol. These results suggest that subchronic treatment with clenbuterol produces a subsensitivity of the beta 2-adrenoceptors and reduced the interaction between beta 2- and alpha 2-adrenoceptors at the vascular wall.