The role of cyclic AMP in the positive inotropic effect mediated by beta 1- and beta 2-adrenoceptors in isolated human right atrium

The time course of the effects of isoprenaline (3 X 10(-7) mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the in...

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Published in:Naunyn-Schmiedeberg's archives of pharmacology 1987-05, Vol.335 (5), p.561-566
Main Authors: Ikezono, K, Michel, M C, Zerkowski, H R, Beckeringh, J J, Brodde, O E
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Adult
Aged
Bisoprolol
Cyclic AMP - metabolism
Cyclic AMP - physiology
Electric Stimulation
Female
Humans
In Vitro Techniques
Isoproterenol - pharmacology
Male
Middle Aged
Myocardial Contraction - drug effects
Myocardium - metabolism
Papaverine - pharmacology
Propanolamines - pharmacology
Propranolol - pharmacology
Receptors, Adrenergic, beta - drug effects
Stimulation, Chemical
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Summary:The time course of the effects of isoprenaline (3 X 10(-7) mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the increase in contractile force. The effects of isoprenaline on contractile force and on the intracellular level of cyclic AMP were enhanced in the presence of the phosphodiesterase inhibitor papaverine (10(-5) mol/l). On the other hand, the beta-adrenoceptor antagonist propranolol (10(-7) mol/l) suppressed isoprenaline-induced cyclic AMP increases, but reduced the increase in force of contraction by only 35%. In addition, both the beta 1-selective antagonist bisoprolol (3 X 10(-9)-3 X 10(-8) mol/l) and the beta 2-selective antagonist ICI 118,551 (3 X 10(-9)-3 X 10(-8) mol/l) inhibited the isoprenaline-induced cyclic AMP increase concentration-dependently; ICI 118,551 produced more pronounced inhibition than bisoprolol. It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by beta 1- and beta 2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclic AMP independent mechanism cannot be ruled out.
ISSN:0028-1298