β-adrenergic receptor desensitization in cardiac hypertrophy and heart failure

Choi, Dong-Ju; Rockman, Howard A.

doi:10.1007/bf02738246

Cited by 19 publications

(11 citation statements)

References 60 publications

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“…Hemodynamic evaluation was performed as described previously (20). Hemodynamic measurements were recorded at baseline and 45 seconds after infusion of incremental doses of isoproterenol (50, 500, and 1,000 pg).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure

Nienaber¹,

Tachibana²,

Prasad³

et al. 2003

J. Clin. Invest.

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. Jeffrey J. Nienaber and Hideo Tachibana contributed equally to this work. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: β-adrenergic receptor (βAR); G protein-coupled receptors (GPCRs); phosphatidylinositol (PtdIns); phosphoinositide kinase domain (PIK); phosphatidylinositol-3,4,5-tri-phosphate (PtdIns-3,4,5-P3); inactive mutant of PI3Kγ (PI3Kγinact); PI3Kγ knockout (PI3Kγ-KO); hemagglutinin (HA); transverse aortic constriction (TAC); left ventricle (LV); PtdIns-3,4,5-tri-phosphate (PIP3); phosphoprotein kinase B (pPKB); phospho-glycogen synthase kinase (pGSK); extracellular signal-regulated kinase (ERK); LV weight/body weight (LVW/BW); isoproterenol (ISO); immunoblotting (IB); c-terminal region of β-adrenergic receptor kinase-1 (βARK1-ct).

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Section: Methodsmentioning

confidence: 99%

Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure

Nienaber¹,

Tachibana²,

Prasad³

et al. 2003

J. Clin. Invest.

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“…Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation Yassine Sassi, 1 Andrea Ahles, 1 Dong-Jiunn Jeffery Truong, 1 Younis Baqi, 2 Sang-Yong Lee, 2 Britta Husse, 3 Jean-Sébastien Hulot, 4,5 Ariana Foinquinos, 6 Thomas Thum, 6,7 Christa E. Müller, 2 Andreas Dendorfer, 3,8 Bernhard Laggerbauer, 1 …”

Section: Extracellular Camp Prevents Adrenergically Induced Cardiac Hmentioning

confidence: 99%

“…Intracellular cAMP formation represents the strongest mechanism for increasing cardiac function, but continuous activation of the cAMP pathway can promote cardiac hypertrophy and fibrosis (i.e., myocardial remodeling) and thereby contribute to cardiac disease (2). To prevent such detrimental consequences of sustained cAMP signaling, the extent and duration of cAMP formation underlie feedback control mechanisms, which include desensitization of βARs or rapid degradation of cAMP (3). In addition, stimulated cells invest a substantial amount of energy into transporting cAMP outside cells, a process that is mediated in mammals by members of the group of ATP-binding cassette (ABC) transporters, in particular, ABCC4, ABCC5, and ABCC11 (also termed MRP4, MRP5, and MRP8, respectively) (4-7).…”

Section: Introductionmentioning

confidence: 99%

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Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

Sassi¹,

Ahles²,

Truong³

et al. 2014

J. Clin. Invest.

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International audienceAcute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues

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“…During the past years, the implications of impaired ␤-AR signaling in the pathophysiology of several cardiovascular disorders were explored in animals as well as in humans. Data from these studies indicate that changes in ␤-AR function are associated with heart failure (6,38), hypertension (13,14), and hypertension complicated with ventricular hypertrophy (2).…”

mentioning

confidence: 99%

Exercise restores β-adrenergic vasorelaxation in aged rat carotid arteries

Leosco

Iaccarino

Cipolletta

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Aging is associated with alterations in β-adrenergic receptor (β-AR) signaling and reduction in cardiovascular responses to β-AR stimulation. Because exercise can attenuate age-related impairment in myocardial β-AR signaling and function, we tested whether training could also exert favorable effects on vascular β-AR responses. We evaluated common carotid artery responsiveness in isolated vessel ring preparations from 8 aged male Wistar-Kyoto (WKY) rats trained for 6 wk in a 5 days/wk swimming protocol, 10 untrained age-matched rats, and 10 young WKY rats. Vessels were preconstricted with phenylephrine (10-6 M), and vasodilation was assessed in response to the β-AR agonist isoproterenol (10-10-3 × 10-8 M), the α2-AR agonist UK-14304 (10-9-10-6 M), the muscarinic receptor agonist ACh (10-9-10-6 M), and nitroprusside (10-8-10-5 M). β-AR density and cytoplasmic β-AR kinase (β-ARK) activity were tested on pooled carotid arteries. β-ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. β-AR, α2-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored β-AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced β-AR number and increased β-ARK activity. Training counterbalanced these phenomena and restored β-AR density and β-ARK activity to levels observed in young rat carotids. Our data indicate that age impairs β-AR vasorelaxation in rat carotid arteries through β-AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in β-ARs and β-ARK. Our data support an important role for β-ARK in vascular β-AR vasorelaxation.

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β-adrenergic receptor desensitization in cardiac hypertrophy and heart failure

Cited by 19 publications

References 60 publications

Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure

Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure

Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

Exercise restores β-adrenergic vasorelaxation in aged rat carotid arteries

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