Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

Liang, Chang‐seng; Frantz, Robert P.; Suematsu, Makoto; Sakamoto, Susumu; Sullebarger, J. Thompson; Fan, Ting; Guthinger, Lisa

doi:10.1161/01.cir.84.1.254

Cited by 28 publications

(17 citation statements)

References 42 publications

(3 reference statements)

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“…Left ventricular dP/dt and dP/dt/P were also decreased, but there was no increase in left atrial pressure. The findings are consistent with what we have reported previously (19,25,31,32). Myocardial contractility of the right ventricle is clearly depressed in the RHF animals, as demonstrated in isolated papillary muscle contraction studies (32,53).…”

Section: Discussionsupporting

confidence: 93%

“…The findings are consistent with what we have reported previously (19,25,31,32). Myocardial contractility of the right ventricle is clearly depressed in the RHF animals, as demonstrated in isolated papillary muscle contraction studies (32,53). However, the assessment of left ventricular contractile function in the RHF animals may be less reliable because the left ventricular dP/dt and peak contractile element velocity can be affected by changes in left ventricular geometry (27) as the right ventricular pressure and volume increase in these animals.…”

Section: Discussionsupporting

confidence: 91%

“…Myocardial ␤-receptor density was measured by specific bindings of [ 3 I]iodocyanopindolol (2,200 Ci/mmol; New England Nuclear), as previously described (32). The maximum number of receptor-binding sites was calculated using the AccuFit saturation two sites program (Lundon Software; Chagrin Falls, OH).…”

Section: Myocardial ␤-Adrenoceptor Binding Assaymentioning

confidence: 99%

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Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

Liang

Himura

Kashiki

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Right heart failure (RHF) is characterized by chamber-specific reductions of myocardial norepinephrine (NE) reuptake, ␤-receptor density, and profiles of cardiac sympathetic nerve ending neurotransmitters. To study the functional linkage between NE uptake and the pre-and postsynaptic changes, we administered desipramine (225 mg/day), a NE uptake inhibitor, to dogs with RHF produced by tricuspid avulsion and progressive pulmonary constriction or sham-operated dogs for 6 wk. Animals receiving no desipramine were studied as controls. We measured myocardial NE uptake activity using [ 3 H]NE, ␤-receptor density by [125 I]iodocyanopindolol, inotropic responses to dobutamine, and noradrenergic terminal neurotransmitter profiles by glyoxylic acid-induced histofluorescence for catecholamines, and immunocytochemical staining for tyrosine hydroxylase and neuropeptide Y. Desipramine decreased myocardial NE uptake activity and had no effect on the resting hemodynamics in both RHF and sham animals but decreased myocardial ␤-adrenoceptor density and ␤-adrenergic inotropic responses in both ventricles of the RHF animals. However, desipramine treatment prevented the reduction of sympathetic neurotransmitter profiles in the failing heart. Our results indicate that NE uptake inhibition facilitates the reduction of myocardial ␤-adrenoceptor density and ␤-adrenergic subsensitivity in RHF, probably by increasing interstitial NE concentrations, but protects the cardiac noradrenergic nerve endings from damage, probably via blockade of NE-derived neurotoxic metabolites into the nerve endings.congestive heart failure; neuronal norepinephrine uptake; tyrosine hydroxylase; neuropeptide Y MYOCARDIAL ␤-adrenoceptors are reduced in number in the failing right ventricles of both animals subjected to tricuspid avulsion and pulmonary artery constriction (19) and patients with primary pulmonary hypertension (8). The correspondent left ventricle showed no changes in myocardial ␤-adrenoceptor density despite exposure to the same elevation of circulating norepinephrine (NE) as the right ventricle. Other studies (2, 56) have also shown that myocardial ␤-adrenoceptor downregulation occurs only in the ventricles with elevated filling pressures, such as in selective left heart failure produced by aortic regurgitation. In contrast, when biventricular heart failure is produced by doxorubicin (56) or rapid ventricular pacing (15), myocardial ␤-adrenoceptor density is reduced in both ventricles. These findings suggest myocardial ␤-receptor changes are caused by local rather than systemic mechanisms in heart failure. Furthermore, because myocardial ␤-receptor density correlates inversely with cardiac interstitial NE concentration (15), we speculate that ␤-receptor downregulation occurs in the failing ventricle where interstitial NE is increased by either an increase in NE release, a decrease in tissue clearance of NE, or both.Increased cardiac NE spillover in heart failure has been well established (18,38). In addition, work from our laboratories (21, 25, 31...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

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Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

Liang

Himura

Kashiki

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Therefore, if cardiac RAS modulation is mediated through mechanical stress, it should only affect gene expression patterns in the RV, whereas a putative RAS-modulating role of soluble factors would be expected to result in parallel changes in both ventricles. (17,18). A separate group of dogs (n = 9) underwent identical surgical procedures; however, neither tricuspid valve avulsion nor pulmonary artery constriction were performed.…”

mentioning

confidence: 99%

“…A separate group of dogs (n = 9) underwent identical surgical procedures; however, neither tricuspid valve avulsion nor pulmonary artery constriction were performed. The animals studied in the present experiments have been the subject of previous reports (17,18 Quantification of mRNAs Encoding Canine 13-Actin, Angiotensinogen, Renin, ACE, Chymase, AT1, and AT2 Receptor, and X. laevis B-Globin Using Competitive PCR. All PCRrelated samples and reagents were diluted in nuclease-free water (Promega) and stored in sterile nuclease-free microcentrifuge tubes (Sarstedt).…”

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confidence: 99%

Local stress, not systemic factors, regulate gene expression of the cardiac renin-angiotensin system in vivo: a comprehensive study of all its components in the dog.

Lee

Liang

Lee

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Local stress, not systemic factors, regulate gene expression of the cardiac renin-angiotensin system in vivo: A comprehensive study of all its components in the dog (heart/heart hypertrophy/gene regulation/heart failure) YOUNG-AE LEE*, CHANG-SENG LIANGt, MIN The renin-angiotensin system (RAS) contributes importantly to the maintenance of acute and chronic hemodynamic homeostasis by affecting the function as well as the structure of the cardiovascular system. In addition to the classically described endocrine (circulating) RAS, a number of organs and tissues have in recent years been found to express components of the RAS, leading to the concept of "local" or "tissueresident" RASs acting, presumably, via paracrine, autocrine, or intracrine pathways. The existence of an endogenous RAS in the heart has been confirmed by the demonstration of expression of the genes coding for angiotensinogen, renin (1), angiotensin converting enzyme (ACE), and angiotensin II receptors (2, 3), and by immunohistochemical demonstration of intracardiac angiotensin I and 11 (4). A second pathway for angiotensin II formation via a highly specific and potent serine protease, chymase, has recently been described in the human and canine heart (5, 6).Angiotensin II has been reported to modulate adaptive growth patterns in cardiac hypertrophy via autocrine or paracrine pathways. Angiotensin II stimulates protein synthesis in cardiomyocytes (7) and in cultured aortic vascular smooth muscle cells (8, 9), and appears to be required for the rapid growth of the neonatal heart (10). Upregulation of left ventricular angiotensinogen and ACE has been described in association with pressure-overload hypertrophy (11) and tachypacing-induced heart failure (12). ACE inhibitors are more effective in reversing or preventing cardiac hypertrophy associated with systemic hypertensive states (13, 14) than other agents with equal hypotensive effects (15). Recent in vitro data indicate that activation of the cardiomyocyte RAS is induced by mechanical stress, and that angiotensin II is an essential mediator of stretch-induced cardiac myocyte hypertrophy (16). So far, no corresponding information assessing the role of mechanical stress versus that -of circulating soluble factors in modulating RAS expression in vivo has been presented. Also, a comprehensive assessment of cardiac RAS gene expression in vivo and in vitro has been precluded because no study so far has examined all components of the cardiac RAS. Thus, the goals of the present work were to study the possible role of local mechanical versus systemic soluble factors in the modulation of cardiac RAS gene expression, and to conduct a comprehensive assessment of cardiac gene expression of all known components of the RAS. We studied a canine model of combined pressure-and volume-overload-induced right ventricular hypertrophy and failure (RVHF). In contrast to left ventricular failure, which invariably also results in some hemodynamic embarrassment and, thus, mechanical stress of the right ventricle (RV) transmit...

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Emergency bypass surgery for failed coronary interventions

Topaz

Salter

Janin

et al. 1997

Cathet. Cardiovasc. Diagn.

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Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

Cited by 28 publications

References 42 publications

Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

Local stress, not systemic factors, regulate gene expression of the cardiac renin-angiotensin system in vivo: a comprehensive study of all its components in the dog.

Emergency bypass surgery for failed coronary interventions

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