Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium

Raum, William J.; Laks, MM; Garner, Daniel; Ikuhara, M. H.; Rs, Swerdloff

doi:10.1152/ajpheart.1984.246.1.h31

Cited by 14 publications

(10 citation statements)

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“…2 and 3, Table 2). Although previous studies suggested that chronic catecholamine administration may improve adrenergic signaling (27), the majority of studies in this area show that the chronic administration of ␤-agonists leads to downregulation of adrenergic signaling (36) and myocardial hypertrophy (7,20,31). These data suggest that the isoproterenol-induced augmentation in myocardial systolic and diastolic function seen in the present study may have been due to myocardial hypertrophy.…”

Section: Isoproterenol and The Myocardium In Sepsiscontrasting

confidence: 48%

Effects of isoproterenol on myocardial structure and function in septic rats

Piper

Myers

et al. 1999

Journal of Applied Physiology

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In this study we sought to determine the effect of sepsis on two sequelae of prolonged (24-h) beta-agonist administration, myocardial hypertrophy and catecholamine-induced cardiotoxicity. Sprague-Dawley rats were randomized to cecal ligation and perforation (CLP) or sham study groups and then further randomized to receive isoproterenol (2.4 mg. kg-1. day-1 iv) or placebo treatment. At 24 h, myocardial function was assessed by using the Langendorff isolated-heart technique or the heart processed for plain light microscopy. We found that 1) sepsis reduced contractile function, indicated by a rightward shift in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002); 2) sepsis-induced myocardial depression was reversed by isoproterenol treatment (isoproterenol effect, P < 0.0001); 3) sepsis reduced, but did not block, isoproterenol-induced myocardial hypertrophy (isoproterenol effect, P < 0.0001); 4) sepsis did not protect the heart from catecholamine-induced tissue injury; 5) the septic heart was protected against the effects of ischemiareperfusion (decreased postreperfusion resting tension, ANOVA with repeated measures, P < 0.01), an effect attenuated by isoproterenol treatment (P < 0.005); and 6) sepsis reduced the incidence of sustained asystole or ventricular fibrillation after ischemia-reperfusion (P < 0.05), an effect also attenuated by isoproterenol treatment (P < 0.01). We conclude that, in sepsis, beta-agonists induce changes in myocardial weight and function consistent with acute myocardial hypertrophy. These changes occur at the expense of significant tissue injury and increased sensitivity to ischemia-reperfusion-induced tissue injury.

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Section: Isoproterenol and The Myocardium In Sepsiscontrasting

confidence: 48%

Effects of isoproterenol on myocardial structure and function in septic rats

Piper

Myers

et al. 1999

Journal of Applied Physiology

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“…In contrast, the density of b 2 -ARs was decreased in all myocardial regions including atria, ventricles, myocardial interstitium, and coronary arterioles. Consistently, chronic noradrenaline infusion produced an increase (+49%) in total density of ventricular b-ARs in dogs, an effect accounted for by increase in low-affinity binding sites [160,170]. These findings however are in disagreement with results of some other studies [162] showing that a similar protocol of noradrenaline administration to dogs produced a decrease rather than an increase in total density of myocardial b-ARs, as well as a reduction in number of b 1 -ARs.…”

Section: Cardiac Electrophysiologymentioning

confidence: 67%

“…Chronic b-AR agonist administration is accompanied by a depletion of myocardial noradrenaline stores [144,[157][158][159][160][161] due to sustained stimulation of the presynaptic noradrenaline release and reduced neuronal noradrenaline re-uptake [157,161,162]. Indeed, it was shown that the rate of 3 H-noradrenaline loss from the microsomal fraction of cardiac myocytes is 3-fold faster in ISO-treated as compared to control rats assuming an abnormal storage of myocardial catecholamines following chronic b-AR activation [157].…”

Section: Basal Cardiac Systolic Functionmentioning

confidence: 99%

“…Interestingly, modifications in myocardial b-ARs profile following chronic infusions of b-AR agonist to dog [160,167] and cat [194] were found to occur in the absence of cardiac hypertrophy. Consistently, monocrotaline-induced cardiac hypertrophy in rats was associated with reduced density of myocardial b-ARs only in animals showing a combination of increased LV weight and markedly elevated plasma noradrenaline levels [195].…”

Section: Cardiac Electrophysiologymentioning

confidence: 99%

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Cardiac hypertrophy induced by sustained β-adrenoreceptor activation: pathophysiological aspects

2007

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Cardiac hypertrophy is promoted by adrenergic over-activation and represents an independent risk factor for cardiovascular morbidity and mortality. The basic knowledge about mechanisms by which sustained adrenergic activation promotes myocardial growth, as well as understanding how structural changes in hypertrophied myocardium could affect myocardial function has been acquired from studies using an animal model of chronic systemic beta-adrenoreceptor agonist administration. Sustained beta-adrenoreceptor activation was shown to enhance the synthesis of myocardial proteins, an effect mediated via stimulation of myocardial growth factors, up-regulation of nuclear proto-oncogenes, induction of cardiac oxidative stress, as well as activation of mitogen-activated protein kinases and phosphatidylinositol 3-kinase. Sustained beta-adrenoreceptor activation contributes to impaired cardiac autonomic regulation as evidenced by blunted parasympathetically-mediated cardiovascular reflexes as well as abnormal storage of myocardial catecholamines. Catecholamine-induced cardiac hypertrophy is associated with reduced contractile responses to adrenergic agonists, an effect attributed to downregulation of myocardial beta-adrenoreceptors, uncoupling of beta-adrenoreceptors and adenylate cyclase, as well as modifications of downstream cAMP-mediated signaling. In compensated cardiac hypertrophy, these changes are associated with preserved or even enhanced basal ventricular systolic function due to increased sarcoplasmic reticulum Ca(2+) content and Ca(2+)-induced sarcoplasmic reticulum Ca(2+) release. The increased availability of Ca(2+) to maintain cardiomyocyte contraction is attributed to prolongation of the action potential due to inhibition of the transient outward potassium current as well as stimulation of the reverse mode of the Na(+)-Ca(2+) exchange. Further progression of cardiac hypertrophy towards heart failure is due to abnormalities in Ca(2+) handling, necrotic myocardial injury, and increased myocardial stiffness due to interstitial fibrosis.

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“…2326 Cardiac sympathetic nerve activity has been speculated to play an important role in the development of ventricular hypertrophy. 27 However, depending on the agent and dose administered, exogenous adrenergic agonists may produce either upregulation 28 or the more classic down-regulation 29 of cardiac /3-adrenergic receptor number in the presence of cardiac hypertrophy. Thus, change in cardiac /3-receptor number may be a function of the nature of the pressure overload (mechanical vs neurogenic) as well as of the duration and intensity of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Preserved cardiac beta-adrenergic sensitivity in early renovascular hypertension.

Davidson

Kawashima²,

Banerjee³

et al. 1987

Hypertension

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SUMMARY To determine the mechanism of blunted sympathetic reflex responses in early renovascular hypertension, we measured inotropic and chronotropic responses of the heart to /3-adrenergic stimulation in vivo and myocardial /3-adrenergic receptor number and adenylate cyclase activity in 10 dogs during an early stage of one-kidney renal hypertension. Mean aortic pressure was higher hi the hypertensive dogs (152 ± 4 mm Hg) than in eight sham-operated dogs (122 ± 1 mm Hg; p < 0.001), but heart rate, cardiac output,' and left atrial pressure did not differ between the two groups. Blood pressure reduction with a direct-acting vasodilator, pinacidil, resulted in marked increases in heart rate (+97 ± 12 beats/mm) and rate of change of left ventricular pressure (dP/dt; +1447 ± 367 mm' Hg/sec) in normotensive dogs but only blunted heart rate (+54 ± 12 beats/min) and minimal left ventricular dP/dt (+376 ± 264 mm Hg/sec) responses in hypertensive dogs. In contrast, intravenously administered isoproterenol produced similar increases in heart rate and left ventricular dP/dt in the two groups. These two groups also did not differ in either left ventricular /3-adrenergic receptor number and affinity or basal, isoproterenol-stimulated, and fluoride-stimulated adenylate cyclase activity. Thus, despite blunted reflex responses to blood pressure reduction, hypertensive dogs showed neither reduction in chronotropic and inotropic responses to direct /3-adrenergic stimulation nor /3-adrenergic desensitization of the myocardium, as assessed by /3-adrenergic receptor number and adenylate cyclase activity. Blunted reflex responses in this model of early hypertension must be due to factors operating at some locus other than the /3-adrenergic receptor-adenylate cyclase complex. Supported in part by Public Health Service Grants HL-07220, HL-30194, and AG-03234 and by a grant from the Genesee Valley Chapter of the American Heart Association, New York Affiliate.Presented in part at the 34th annual meeting of the American College of Cardiology at Anaheim, California, March 12, 1985.Address for reprints: Chang-seng Liang, M.D., Ph.D., Cardiology Research Laboratories, Box679, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642.Received August 11, 1986; accepted October 15, 1986. in animals with established renovascular hypertension 2 ' 3 and correlated with reduced myocardial /3-adrenergic receptor number. 43 However, whether similar changes occur during early hypertension is not known. The purpose of the present study was to determine whether myocardial /3-adrenergic desensitization contributed to the blunted reflex responses observed in early renal hypertension. Experiments were performed in two groups of chronically instrumented dogs, soon after the establishment of one-kidney renal hypertension in one group and sham operations in the other normotensive control group. We measured responses of heart rate and rate of left ventricular pressure rise (left ventricular dP/dt) to isoproterenol and to pinacidil, a d...

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Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium

Cited by 14 publications

References 0 publications

Effects of isoproterenol on myocardial structure and function in septic rats

Effects of isoproterenol on myocardial structure and function in septic rats

Cardiac hypertrophy induced by sustained β-adrenoreceptor activation: pathophysiological aspects

Preserved cardiac beta-adrenergic sensitivity in early renovascular hypertension.

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