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

Endoh, Masao; Schümann, Hans-Joachim

doi:10.1007/bf00500039

Cited by 112 publications

(23 citation statements)

References 13 publications

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“…For example, Endoh and Schumann 17 showed that methoxamine produced a negative inotropic effect in rabbit papillary muscle only during relatively rapid (1.5 Hz) stimulation, and we found that epinephrine plus propranolol produced a negative inotropic effect only if the hearts were perfused with buffer containing 2.0 or 2.5 mM Ca 2+ , a level about twice the physiological concentration in rats.…”

Section: Discussionsupporting

confidence: 51%

“…As previously mentioned, several other investigators have also demonstrated a negative inotropic and chronotropic effect of a-adrenergic receptor stimulation on whole hearts. 6 " 8 - 13 - 16 ' 17 Recently, Posner and co-workers 37 and Danilo and colleagues 38 showed that activation of a-adrenergic receptors decreased spontaneous rates of isolated dog Purkinje fibers. Taken together, these diverse studies indicate that activation of a-adrenergic receptors can, under certain conditions, lead to a functional depression of cardiac tissue.…”

Section: Discussionmentioning

confidence: 99%

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alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.

Watanabe

Hathaway

Besch

et al. 1977

Circulation Research

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SUMMARY We determined the effect of a-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of a-adrenergic receptors with either phenylephrine (10~8 M to 10~6 M) or epinephrine (10" M to 10~6 M) plus propranolol (10 ' ! M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10~6 M). Phenylephrine (10 s M) attenuated cyclic AMP generation in response to isoproterenol (10" s M and 10 s M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10 (i M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by /3-adrenergic receptors, whereas decreases appear to be mediated by a-adrenergic receptors. IN 1967, Robison et al. 1 hypothesized that activation of either a-adrenergic or /3-adrenergic receptors may modify the activity of adenylate cyclase and result in changes in the rate of conversion of ATP to cyclic adenosine monophosphate (cyclic AMP). They further predicted that asympathomimetic agents could induce a decrease in the activity of the enzyme in some tissues. This original hypothesis has since been corroborated by studies which indicate that some a-adrenergic effects are mediated by a reduction in the tissue level of cyclic AMP. 2 " 5 Although there is an abundance of evidence that activation of a-adrenergic receptors can lead to alterations in the electrophysiological and mechanical functions of the heart, 6 " 18 no intracellular mediator or biochemical basis for these effects has been identified. It has been fairly convincingly shown that these a-adrenergic effects are not mediated by an increase in myocardial cyclic AMP concentrations. 1920 The question remains, however, whether any of the a-adrenergic effects on the heart might be mediated by a decrease in tissue cyclic AMP levels. The purpose of the present study was to attempt to demonstrate whether stimulation of myocardial a-adrenergic receptors is associated with a fall in cyclic AMP concentrations. The studies were carried out using isolated adult rat heart cells. To extend the findings to the intact heart, we also performed a limited parallel study of a-adrenergic effects on contractility and cyclic AMP levels of isolated, perfused rat hearts. Methods ISOLATION OF CELLSOur me...

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.

Watanabe

Hathaway

Besch

et al. 1977

Circulation Research

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“…However, several studies have described the appearance of a decrease in contractile force with treatment of a-adrenoceptor agonists in the artial and/or ventricular muscles of rats (1,(8)(9)(10), rabbits (5,11,12), and bullfrogs (13), although it does not always follow that the observed nenative inntrnnin effect was confirmed to be specifically mediated by a-adrenoceptors.…”

Section: Abstract-influencesmentioning

confidence: 99%

Differential influences of several .ALPHA.-adrenoceptor antagonists on .ALPHA.-adrenoceptor-mediated inotropic responses in the left atria of guinea pigs.

Hattori

Kanno

1982

Jpn.J.Pharmacol

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“…Since it has been shown that the positive inotropic action elicited by stimulation of a-adrenoceptors in the mammalian heart depends very much on the experimental conditions (Nakashima et al, 1973;Endoh & Schumann, 1975a;Endoh, et al, 1975;Ledda et al, 1975;Mugelli et al, 1976;Kunos, 1977;Kunos & Nickerson, 1977), in this study the ventricular myocardium and sinus node of the dog were maintained under near physiological conditions (Endoh, 1975) by perfusing with arterial blood from a donor dog. The actions of PE were then compared with those of Iso.…”

Section: Blood-perfused Preparationsmentioning

confidence: 99%

“…The influence of temperature, stimulation frequency, phosphodiesterase inhibition and of a-and f-adrenoceptor blocking agents on phenylephrine-induced myocardial stimulation were investigated. These interventions have been shown to be useful in differentiating the role of ax-and f0-adrenoceptors in the rabbit and guinea-pig heart (Schumann, et al, 1974;Endoh & Schumann, 1975a;Endoh, Wagner & Schumann, 1975;Ledda, Marchetti & Mugelli, 1975;Mugelli, Ledda & Mantelli, 1976).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Adrenoceptors Mediating Positive Inotropic Responses in the Ventricular Myocardium of the Dog

Endoh

Shimizu

Yanagisawa

1978

British J Pharmacology

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1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood-perfused papillary muscles and isolated strips of ventricular myocardium. 2 On the blood-perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose-response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose-response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline.3 The infusion of pindolol, a P-adrenoceptor blocking agent, at a rate of 1 1±g/min, shifted the isoprenaline dose-response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine. 4 On isolated ventricular strips a-adrenoceptor blockade by 10-6M phentolamine did not affect dose-response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose-response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner. 5 On ventricular strips from reserpine-pretreated dogs phenylephrine and tyramine dose-response curves were shifted markedly to the right and downwards. Desipramine (10-5M) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine.6 Papaverine (10' M) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose-response curves to the left. 7 Raising the temperature from 32°C to 37°C shifted phenylephrine dose-response curves to the right; when the temperature was raised from 37°C to 42°C the affinity of the drug was not changed.8 Other a-adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 x 10-'M) were not affected by phentolamine (10-6 M).9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the P-type and that post-synaptic a-adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on ,B-adrenoceptors.

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

Cited by 112 publications

References 13 publications

alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.

alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.

Differential influences of several .ALPHA.-adrenoceptor antagonists on .ALPHA.-adrenoceptor-mediated inotropic responses in the left atria of guinea pigs.

Characterization of Adrenoceptors Mediating Positive Inotropic Responses in the Ventricular Myocardium of the Dog

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