Further evidence of interaction between vasodilator beta 2- and vasoconstrictor alpha 2-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats.
The importance of the interaction of alpha- and beta-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 beta 2-adrenoceptor antagonist ICI 118.551 was more effective in antagonizing isoproterenol-induced hypotension (mainly beta 2-mediated) than tachycardia (mainly beta 1-mediated). Intravenous (i.v.) administration of the alpha 2-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 beta-adrenoceptor antagonist propranolol, but not by metoprolol, a more selective beta 1-blocker. Fourteen days of administration of the beta 2-adrenoceptor agonist CLEN [0.3 mg/kg, subcutaneously (s.c.) twice daily], a treatment that induces desensitization of beta 2-mediated vasodilation, increased the pressor response induced by CLO, an effect that was not observed in pentobarbital-anesthetized rats. In any case, neither beta-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 alpha 2- and beta 2-adrenoceptor-mediated responses in rat vasculature and suggest that vasodilator beta 2-adrenoceptors might contribute to the determination of peripheral vascular tone when circulating EPI is substantially elevated.
Kazanietz
M G
MG
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, UBA, Argentina.
Gutkind
J S
JS
Puyo
A
A
Armando
I
I
Enero
M A
MA
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002976:Clenbuterol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D002395:Catecholamines; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D007545:Isoproterenol; D002976:Clenbuterol