Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta2 adrenoceptors in the sinoatrial node

Db, Friedman; Ti, Musch; Williams, Robert R.; Ga, Ordway

doi:10.1093/cvr/21.2.124

Cited by 17 publications

(11 citation statements)

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“…However, it does not mean such stimulation of the re ceptors to be physiological relevant (24). The effects of atenolol and propranolol were studied on the hemody namic responses induced by exercise in dogs and sug gested that ,82-adrenoceptors in the SA node might be stimulated by circulating catecholamines and contri buted greatly to sympathetic modulation of HR during heavy exercise in dogs (6). It was shown that failing hu man ventricular myocardium contained a relative high proportion of X82-adrenoceptors, due to selective down regulation of ,81-adrenoceptors using a radioligand binding study (25).…”

Section: Discussionmentioning

confidence: 99%

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Sympathetic Nerve Stimulation Activates Both β1 and β2-Adrenoceptors of SA and AV Nodes in Anesthetized Dog Hearts

Takei

Furukawa

Narita

et al. 1992

Japanese Journal of Pharmacology

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We investigated blocking effects of the selective 8 1-adrenoceptor blocker atenolol (0.1 100 ,ug/kg, i.v.), the selective fl2-adrenoceptor blocker ICI 118,551 (1-1000 ,ug/kg, i.v.) and the com bination of the two drugs on positive chronotropic and dromotropic responses to norepinephrine (NE) released by stimulation of the sympathetic nerves in anesthetized, neurally decentralized, open-chest dogs after atropine was given. Stimulation of the intracardiac sympathetic nerves to the SA nodal re gion or to the AV nodal region selectively increased heart rate or decreased AV conduction time, re spectively. ICI 118,551 inhibited the chronotropic or dromotropic response to each stimulation in a dose-dependent manner, but its inhibition of the dromotropic response was less than that of the chro notropic response. Atenolol similarly inhibited either the positive chronotropic or dromotropic response to each stimulation in a dose-related manner. The combination of atenolol and ICI 118,551 attenuated the responses to each stimulation more than atenolol alone. These data indicate that sympathetic nerve stimulation activates both 81 and 82-adrenoceptors of the SA and AV nodes and that the proportion of ,62-adrenoceptor-mediated effects on the AV node is less than that on the SA node. These results suggest that neurally released NE in part controls physiological functional cardiac responses mediated through 82-adrenoceptors, in addition to the responses predominantly mediated through ~' 1-adreno ceptors.

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Section: Discussionmentioning

confidence: 99%

“…NE is pos tulated as a selective 8 1-adrenoceptor agonist to / adrenoceptors (2 5), although it has been suggested that circulating catecholamines cause a positive chrono tropic effect mediated by ,E2-adrenoceptors in the ex ercising dog (6).…”

mentioning

confidence: 99%

Sympathetic Nerve Stimulation Activates Both β1 and β2-Adrenoceptors of SA and AV Nodes in Anesthetized Dog Hearts

Takei

Furukawa

Narita

et al. 1992

Japanese Journal of Pharmacology

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“…5). Although Lands et al (32,33) first subclassified beta adrenoceptors into beta-1 and beta-2 sub types with absolute organ-specific distribu tion such as beta-1 receptors in the heart and beta-2 receptors in the lung, it has been sug gested that both receptor subtypes exert a physiological role in the cat, dog and human hearts from pharmacological (20,34,35), biochemical (30,36,37) and receptor-bind ing studies (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological analysis of positive chrono- and inotropic responses to denopamine (TA-064) in dog cross-circulated atrial and ventricular preparations.

et al. 1990

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Abstract-Positive chrono and inotropic responses to denopamine (TA-064, (-) (R)-1-(p-hydroxyphenyl)-2- [(3,4-dimethoxyphenethyl)amino] ethanol), a new and orally active cardiotonic agent, were investigated in the canine isolated right atrial or left ventricular preparation which was cross-circulated with blood from another support dog. Denopamine dose-dependently increased the sinus rate, right atrial and left ventricular contractile force. Denopamine was one to two orders of mag nitude less potent than isoproterenol. The positive chrono and inotropic effects of denopamine in isolated, blood-perfused right atria were dose-dependently in hibited by treatment with propranolol and atenolol. The effects of denopamine were only slightly attenuated by ICI 118,551 in doses which completely suppressed the positive chrono and inotropic effects of procaterol. The increases in sinus rate and atrial contractility induced by denopamine were partially but significantly attenuated by treatment with imipramine in a dose which suppressed the effects of tyramine and potentiated the effects of norepinephrine. These results indicate that denopamine is a highly selective beta-1 adrenoceptor agonist in isolated, blood perfused dog heart preparations, and they also suggest a mild catecholamine releasing activity through tyramine-like action in isolated right atria.Congestive heart failure is characterized by a state of insufficient cardiac output to fulfill the metabolic requirements of the body. One of the therapies for congestive heart failure is augmenting the cardiac pumping function (positive Inotropic action). Cardiac gly cosides are the drugs used for producing Positive inotropic effects, but their effec tiveness and safety remain controversial be cause of their toxicity. Some catecholamines such as dopamine and dobutamine, which have a strong positive inotropic effect, are clinically available only by intravenous ad ministrations. Therefore, potent positive Ino tropic drugs which are orally active and pos sess a wide margin of safety are of great interest in the treatment of heart failure.Recently, orally active positive Inotropic com pounds have been developed which have beta -sympathom1metic (1-4) or phosphodies terase inhibiting action (5-9), and these agents are structurally unrelated to cardiac gly cosides. Denopamine, a newly synthesized phenylethanolamine derivative, is the former type of cardiotonic agent. Ikeo et al. (10) have reported that, administered parenterally or orally, denopamine induced a significant dose-dependent increase in contractile force and dp/dtmax in the left ventricle with a little change in heart rate in anesthetized and con scious dogs.The cardiotonic effects of denopamine with a weak arrhythmogenic ac tivity were also demonstrated in guinea pigs, rabbits, cats, monkeys, rats and pigs (11)(12)(13)(14). Kino et al. (15) have revealed that the in travenous infusion of denopamine produced a To whom correspondence should be addressed.marked increase in dp/dtmax in the left ventri cle without sig...

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“…Accordingly, the reduction in peak heart rate response by non-selective ,B-adrenoceptor blockers may be due to blockade of the 12-as well as 13l-adrenoceptors (Friedman et al, 1987). This may be a limitation in the use of exercise induced tachycardia for comparison of equipotent doses of 13-adrenoceptor antagonists with respect to 13l-mediated responses.…”

Section: Heart Ratementioning

confidence: 99%

“…Both ,B-selective and non-selective 3-adrenoceptor antagonists augment adrenaline levels during exercise (Gullestad et al, 1989b;Irving et al, 1971), and this may stimulate 132-adrenoceptors in the myocardium directly at maximal exercise. Accordingly, the reduction in peak heart rate response by non-selective ,B-adrenoceptor blockers may be due to blockade of the 12as well as 13l-adrenoceptors (Friedman et al, 1987). This may be a limitation in the use of exercise induced tachycardia for comparison of equipotent doses of 13-adrenoceptor antagonists with respect to 13l-mediated responses.…”

Section: Heart Ratementioning

confidence: 99%

Effects of selective beta 2‐adrenoceptor blockade on serum potassium and exercise performance in normal men.

Gullestad

Birkeland

Nordby

et al. 1991

Brit J Clinical Pharma

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3 Cumulative work was significantly reduced by ICI-118551 (6.4%, P = 0.04) and by propranolol (12.4%, P < 0.01), whereas the reduction with atenolol (5.6%) did not reach statistical significance. 4 Atenolol and propranolol reduced peak heart rate by 23% and 29%, and peak systolic blood pressure by 9% and 11% respectively during maximal exercise. ICI-118551 caused a non-significant reduction in heart rate during submaximal exercise, with a significant reduction at maximum exercise (6% reduction), whereas systolic blood pressure was not different from placebo. Diastolic blood pressures were similar across all treatment regimens. 5 Similar glucose concentrations were obtained at baseline and at exhaustion during all treatment regimens. Lactate concentrations were comparable for any given exercise intensity irrespective of treatment regimens. Propranolol reduced lactate concentrations from the exercising muscles at maximum exercise in proportion to the reduction of maximal exercise capacity.6 The subjective perception of fatigue was not affected by either 13l-or P2-adrenoceptor blockade.7 In a separate study, the effects of selective P2-adrenoceptor stimulation (terbutaline) in resting men on heart rate, systolic blood pressure, serum potassium and glucose were completely blocked by the doses of ICI-118551 used in the exercise study.8 We conclude that both ,l-and ,32-adrenoceptors are of importance for maximal short term exercise performance in healthy young men. The decisive mechanism for the reduction in exercise performance during ,-adrenoceptor blockade is unclear.The present study suggests that other mechanisms than haemodynamic and metabolic factors are of importance. The lack of effect of selective ,32-adrenoceptor antagonists on serum potassium at rest and during exercise, and the finding that the rate of decline in the potassium concentrations after exhaustion was independent of treatment regimens, suggests that ,3-adrenoceptors are of minor importance for potassium release or reuptake in the exercising muscle.

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Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta2 adrenoceptors in the sinoatrial node

Cited by 17 publications

References 0 publications

Sympathetic Nerve Stimulation Activates Both β1 and β2-Adrenoceptors of SA and AV Nodes in Anesthetized Dog Hearts

Sympathetic Nerve Stimulation Activates Both β1 and β2-Adrenoceptors of SA and AV Nodes in Anesthetized Dog Hearts

Pharmacological analysis of positive chrono- and inotropic responses to denopamine (TA-064) in dog cross-circulated atrial and ventricular preparations.

Effects of selective beta 2‐adrenoceptor blockade on serum potassium and exercise performance in normal men.

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