Lack of correlation between the positive inotropic effect evoked by α-adrenoceptor stimulation and the levels of cyclic AMP and/or cyclic GMP in the isolated ventricle strip of the rabbit

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Abstract

In electrically driven isolated right ventricle strips of the rabbit, phentolamine (10−6 m) shifted the dose-response curve for the positive inotropic effect of phenylephrine by about 1.0 log unit to the right, whereas pindolol (3 × 10−8 m) shifted only its upper part to the right. Under the blockade of β-adrenoceptors by 3 × 10−8 m pindolol, phenylephrine (3 × 10−5 m) increased the contractile force of the ventricular strips without changing the levels of cAMP and cGMP; inhibition of the phosphodiesterase by papaverine (10−5 m) did not influence these effects of phenylephrine. Isoprenaline (3 × 10−7 m) produced a rise of the cAMP-content preceding the increase of the contractile force; the cGMP-level, however, remained unchanged. 10−6 m phenylephrine, a concentration, which stimulates predominantly α-adrenoceptors, did not influence the effects evoked by isoprenaline. From the present results it is concluded, that in the ventricular myocardium of the rabbit there exist α-adrenoceptors mediating the positive inotropic effect and that the stimulation of α-adrenoceptors does not influence the cAMP- and cGMP-generating system, neither its basal nor its stimulated activity.

References (38)

  • M. Endoh et al.

    Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by α-adrenoceptors in the isolated rabbit papillary muscle

    Naunyn-Schmiedeberg's Archives of Pharmacology

    (1975)
  • M. Endoh et al.

    Influence of temperature on the positive inotropic effects mediated by α- and β-adrenoceptors in the isolated rabbit papillary muscle

    Naunyn-Schmiedeberg's Archives of Pharmacology

    (1975)
  • M. Endoh et al.

    Relationship between the level of cAMP and the contractile force under stimulation of α- and β-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle

    Naunyn-Schmiedeberg's Archives of Pharmacology

    (1976)
  • W.J. George et al.

    Elevation of guanosine 3′,5′-cyclic phosphate in rat heart after perfusion with acetylcholine

  • W.J. George et al.

    Influence of acetylcholine on contractile force and cyclic nucleotide levels in the isolated perfused rat heart

    Journal of Pharmacology and Experimental Therapeutics

    (1973)
  • W.J. George et al.

    Opposing regulatory influences of cyclic guanosine monophosphate and cyclic adenosine monophosphate in the control of cardiac muscle contraction

  • A.G. Gilamn

    A protein binding assay for adenosine 3′,5′-cyclic monophosphate

  • N.D. Goldberg et al.

    The biological role of cyclic 3′,5′-guanosine monophosphate

  • N.D. Goldberg et al.

    Biologic regulation through opposing influence of cyclic GMP and cyclic AMP: the Yin Yang hypothesis

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    This work was supported by the Deutsche Forschungsgemeinschaft.

    Permanent address: Department of Pharmacology, Tohoku University School of Medicine, 980 Sendai, Japan.

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