Failing of left ventricular β adrenergic affinity in a canine model of obesity-hypertension

Cabrol, Philippe; Gallnier, M.; Fourcade, J; Léger, Philippe; Montastruc, Jean‐Louis; Bounhoure, Jean-Paul; Fauvel, Jean–Marie; Senard, J. M.

doi:10.1016/s0735-1097(98)80277-5

Cited by 4 publications

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“…These results suggest that despite an unmodified b adrenergic system in diet-induced obesity models, the cardiovascular changes can be partly explained by insulin-related parasympathetic dysfunction. 30,31 Heterologous regulation of the M 2 R has not been extensively studied and the mechanisms involved are not entirely characterized. 32 Many factors such as cytokines and trophic factors (ie insulin, growth hormone) could potentially modify M 2 R expression via transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Insulin downregulates M2-muscarinic receptors in adult rat atrial cardiomyocytes: a link between obesity and cardiovascular complications

et al. 2004

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OBJECTIVE:To determine whether decreased cardiac parasympathetic activity observed in obesity is due to insulin-induced alterations in cardiac M 2 -muscarinic receptors and/or adenylyl cyclase activity. DESIGN AND METHODS: After incubation with increasing concentrations of insulin, adult rat atrial cardiomyocytes were assayed for M 2 -muscarinic receptor binding density and affinity, and for M 2 R mRNA expression using RT-PCR analysis. Forskolinstimulated adenylyl cyclase activity and its inhibition by carbachol were also assayed, as was endothelial nitric oxide synthase mRNA expression. The effects of insulin on M 2 -muscarinic receptor density and mRNA expression levels were analyzed using the insulin signaling inhibitors rapamycin, wortmanin and PD 098059. RESULTS: Insulin induces a concentration-and time-dependent decrease in expression of the M 2 R mRNA, and in [ 3 H]Nmethylscopolamine binding by the receptor. These effects on the M 2 R mRNA levels and on [ 3 H]N-methylscopolamine binding were prevented by PD 98059, but not by wortmanin or rapamycin. Basal and forskolin-induced cAMP production did not differ, but the inhibition of forskolin-simulated enzyme activity by carbachol was blunted by insulin. No change in the mRNA levels for endothelial nitric oxide synthase was observed. CONCLUSION: In rat atrial cardiomyocytes, insulin markedly alters both the M 2 -muscarinc receptor density, and its mRNA expression through transcriptional regulation and adenylyl cyclase activity. These data suggest that the obesity-associated decrease in cardiac parasympathetic tone may be related to hyperinsulinemia, which could directly contribute to cardiovascular morbidity in obese patients.

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Section: Discussionmentioning

confidence: 99%

Insulin downregulates M2-muscarinic receptors in adult rat atrial cardiomyocytes: a link between obesity and cardiovascular complications

et al. 2004

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“…Sympathetic β‐adrenoceptor dysfunction may also contribute to the coronary dysfunction in the metabolic syndrome as obesity is associated with reduced cardiac β‐adrenoceptor density [ 96 , 195 ], affinity [ 96 ], and post receptor signaling mechanisms [ 27 , 30 , 31 ]. We postulate that these changes could result in a reduction of β‐adrenoceptor mediated coronary vasodilation, an important mediator of functional coronary hyperemia [ 53 , 81 , 141 ], but at present no studies have directly addressed this hypothesis.…”

Section: Neurohumoral Control Of Coronary Flow In Obesity and Insulinmentioning

confidence: 99%

Mechanisms of Coronary Dysfunction in Obesity and Insulin Resistance

et al. 2007

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The incidence of obesity and the metabolic syndrome has reached epidemic proportions and alterations in coronary microvascular function could contribute to the increased cardiovascular morbidity and mortality observed in these patients. This review highlights key mechanisms of impaired control of coronary blood flow in the metabolic syndrome. Specifically, coronary endothelial dysfunction, altered neurohumoral control, and the potential roles of smooth muscle ion channels are addressed. Recent studies indicate that alterations in endothelial-dependent vasodilation or endothelial-dependent vasoconstriction contribute little to obesity-induced impairments in coronary vascular control. In contrast, augmented vasoconstriction in response to neurohumoral mediators appears to play a significant role in coronary vascular dysfunction. The authors conclude that coronary dysfunction in the metabolic syndrome is characterized by an imbalance between coronary blood flow and myocardial metabolism that may be mediated by sensitization of vasoconstrictor pathways. Further, they suggest that alterations in smooth muscle ion channels, Ca(2+) handling, and cell signaling may be important mechanisms leading to coronary microvascular dysfunction. Importantly, however, more research is needed to clearly delineate specific mechanisms and identify potential therapeutic targets.

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“…In this sense a specific desensitisation of left ventricular ␤-adrenoceptors independent of plasma noradrenaline levels has been reported in a model of obesity and hypertension in dogs. 38 The inverse relationship observed between left ventricular mass index and ␤ 2 -adrenoceptor density and response suggests that left ventricular hypertrophy in essential hypertension, as occurs in other diseases, is associated to a ␤ 2 -adrenoceptor down-regulation and a decreased ␤ 2 adrenoceptor function, probably as a compensating mechanism of the hypertrophied myocardiocyte, secondary to the sympathetic nervous system overactivity reported in young essential hypertensive patients.…”

Section: Discussionmentioning

confidence: 97%

β-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives

et al. 2000

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A sympathetic overactivity has been reported in the early stages of essential hypertension and has been involved in the pathogenesis of left ventricular hypertrophy (LVH) in essential hypertension. The state of ␤ 2 -adrenergic receptors as related to the presence of this complication was investigated in a group of 15 essential hypertensive patients and compared to 10 normotensive control subjects. Left ventricular mass index was determined by bidimensional echocardiography. Plasma catecholamine levels were measured by a radioenzymatic assay. ␤ 2 -adrenoceptor density was measured in intact lymphocytes by radioligand binding assay, using the hydrophilic ligand CGP 12177. ␤ 2 -adrenoceptor function was assessed by measuring intracellular cAMP levels in isoproterenol-stimulated lymphocytes. Left ventricular mass index (P Ͻ 0.05),

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Failing of left ventricular β adrenergic affinity in a canine model of obesity-hypertension

Cited by 4 publications

References 0 publications

Insulin downregulates M2-muscarinic receptors in adult rat atrial cardiomyocytes: a link between obesity and cardiovascular complications

Insulin downregulates M2-muscarinic receptors in adult rat atrial cardiomyocytes: a link between obesity and cardiovascular complications

Mechanisms of Coronary Dysfunction in Obesity and Insulin Resistance

β-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives

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