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Impaired Atrial M2-Cholinoceptor Function in Obesity-Related Hypertension

Pelat, Michel and Verwaerde, Patrick and Mérial, Christelle and Galitzky, Jean and Berlan, Michel and Montastruc, Jean-Louis and Senard, Jean-Michel Impaired Atrial M2-Cholinoceptor Function in Obesity-Related Hypertension. (1999) Hypertension, 3 (5). 1066-1072. ISSN 0194-911X

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Official URL: http://hyper.ahajournals.org/cgi/content/full/34/5/1066


The aim of this study was to investigate the activity of the parasympathetic limb of the baroreflex arch in a canine model of obesity-related hypertension. Twelve male beagle dogs were randomized into 2 groups. Six dogs were fed with normal canine food and 6 were submitted to a 10-week high-fat diet (HFD). We have evaluated the consequences of HFD on heart rate (HR) and blood pressure (BP) circadian cycles and methylscopolamine dose-response curves. Binding of [3H]-AF-DX 384 and adenylyl cyclase activity were investigated to determine the density and functionality of M2-cholinoceptors on right atrial membranes from control and HFD dogs. HFD induced a significant increase in body weight (1561 vs 1261 kg), systolic BP (16165 vs 14564 mm Hg), diastolic BP (9263 vs 7962 mm Hg), and HR (9664 vs 8163 bpm). Circadian rhythms of HR and BP observed in the baseline period were abolished after 9 weeks of HFD. After propranolol (1 mg/kg) pretreatment, the dose of methylscopolamine able to induce 50% maximum tachycardia was significantly increased after 9 weeks of HFD (7.460.3 vs 4.760.1 mg/kg). In the control group, the experimental period failed to modify these parameters. The numbers of M2-cholinoceptors measured in right atrial membranes were significantly lower in HFD than in control groups (5466 vs 2766 fmol/mg protein). The ability of carbachol to inhibit isoproterenol-stimulated adenylyl cyclase activity was significantly lower in HFD than in control groups (IC50547612 vs 6.461.4 mmol/L). However, the basal activity of adenylyl cyclase was unchanged by HFD. HFD decreases M2-cholinoceptor number and function in cardiomyocytes. This could explain the abolition of circadian rhythm of HR and the changes in chronotropic effect brought about by methylscopolamine.

Item Type:Article
Additional Information:L'éditeur n'autorise pas la mise en ligne de l'article.
Audience (journal):International peer-reviewed journal
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Institution:French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
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Deposited On:03 Jun 2010 14:03

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