ArticleCardiovascular research2007
Heterozygous alpha 2C-adrenoceptor-deficient mice develop heart failure after transverse aortic constriction.
Article in Cardiovascular research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 43 citations in OpenAlex.
- Alpha2-adrenoceptors in adrenomedullary chromaffin cells: functional role and pathophysiological implications.Pflugers Archiv : European journal of physiology · 2018Review
- Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes.Immunity & ageing : I & A · 2013Article
- Are the pharmacology and physiology of α₂ adrenoceptors determined by α₂-heteroreceptors and autoreceptors respectively?British journal of pharmacology · 2012Review
- Subcoronary versus supracoronary aortic stenosis. An experimental evaluation.Journal of cardiothoracic surgery · 2011Article
- Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.British journal of pharmacology · 2010Article
- Transgenic simulation of human heart failure-like L-type Ca2+-channels: implications for fibrosis and heart rate in mice.Cardiovascular research · 2009Article
- Beta-adrenergic stimulation and myocardial function in the failing heart.Heart failure reviews · 2009Review
- Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice.The Journal of clinical investigation · 2009Article
- Endothelium-specific overexpression of human IC53 downregulates endothelial nitric oxide synthase activity and elevates systolic blood pressure in mice.Cardiovascular research · 2009Article
- Modulation of alpha2-adrenoceptor functions by heterotrimeric Galphai protein isoforms.The Journal of pharmacology and experimental therapeutics · 2009Article
- Mechanisms of pharmacogenomic effects of genetic variation within the cardiac adrenergic network in heart failure.Molecular pharmacology · 2009Review
- Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival.BMC medical genetics · 2008Article
- Tight control of adrenal medulla catecholamine release by alpha 2C-adrenergic receptors influences susceptibility to heart failure.Cardiovascular research · 2007Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveFeedback regulation of norepinephrine release from sympathetic nerves is essential to control blood pressure, heart rate and contractility. Recent experiments in gene-targeted mice have suggested that alpha(2C)-adrenoceptors may operate in a similar feedback mechanism to control the release of epinephrine from the adrenal medulla. As heterozygous polymorphisms in the human alpha(2C)-adrenoceptor gene have been associated with cardiovascular disease including hypertension and chronic heart failure, we have sought to characterize the relevance of alpha(2C)-gene copy number for feedback control of epinephrine release in gene-targeted mice.
methodsAdrenal catecholamine release, basal hemodynamics and susceptibility to develop heart failure after transverse aortic constriction were tested in mice with two copies (+/+), one copy (+/-) or no functional alpha(2C)-adrenoceptor gene (alpha(2C)-/-).
resultsHeterozygous alpha(2C)-receptor deletion (alpha(2C)+/-) resulted in a 43% reduction of adrenal alpha(2C) mRNA copy number and in a similar decrease in alpha(2)-receptor-mediated inhibition of catecholamine release from isolated adrenal glands in vitro. Urinary excretion of epinephrine was increased by 74+/-15% in alpha(2C)+/- and by 142+/-23% in alpha(2C)-/- mice as compared with wild-type control mice. Telemetric determination of cardiovascular function revealed significant tachycardia but no hypertension in alpha(2C)-adrenoceptor-deficient mice. alpha(2C)+/- mice were more susceptible to develop cardiac hypertrophy, failure and mortality after left-ventricular pressure overload than alpha(2C)+/+ mice.
conclusionAdrenal alpha(2)-mediated feedback regulation of epinephrine secretion differs fundamentally from sympathetic feedback control. A single adrenoceptor subtype, alpha(2C), operates without a significant receptor reserve to prevent elevation of circulating epinephrine levels. This genetic model may provide an experimental basis to study the pathophysiology of alpha(2C)-adrenoceptor dysfunction in humans.
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