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 inhibit...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 251; no. 3; pp. 884 - 887 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.12.1989
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |