Effect of clonidine on myocardial cyclic GMP content in the mouse-activation of central and peripheral alpha adrenoceptors.
Clonidine (0.23-3.77 mumol/kg i.p.) produced a dose-dependent increase in mouse myocardial cyclic GMP (cGMP) content. This effect was antagonized by yohimbine (0.03-1 mg/kg i.p.), but not by prazosin (1 mg/kg i.p.). The inhibition by yohimbine was biphasic. The cGMP response to clonidine was inhibited by atropine (5 mg/kg i.p.) and methylatropine (0.2-5 mg/kg i.p.). In mice pretreated with the ganglionic blocker hexamethonium, the cGMP response to clonidine persisted. St-91 [(2,6-diethylphenylamino)-2-imidazoline] (0.39-3.94 mumol/kg i.p.), a cogener of clonidine which does not cross the blood-brain barrier, also increased myocardial cGMP content. The potency of clonidine was similar in mice pretreated and nonpretreated with hexamethonium. Methylatropine did not affect the cGMP response to St-91 and to clonidine in ganglionectomized mice and yohimbine was a less potent antagonist. These results indicate that systemic administration of clonidine produces an increase in myocardial cGMP content by both a central and a peripheral action. The increase in cGMP can be due to a direct activation of cardiac prejunctional alpha-2 adrenoceptors and to stimulation of cardiac muscarinic receptors, a response secondary to an action of clonidine on central alpha-2 adrenoceptors.
Vulliemoz
Y
Y
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York.
Verosky
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000032:analysis*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects
D006584:Hexamethonium Compounds; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D018738:Hexamethonium; C011266:ST 91; D006152:Cyclic GMP; D003000:Clonidine