Myocardial beta-adrenergic reactivity in pressure overload-induced cardiac hypertrophy in the rat.
The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol and the beta (1)/beta (2)-adrenoceptor ratio were estimated. Four weeks of cardiac pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.
Communal
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Laboratoire de Pharmacologie Cardiovasculaire Expérimentale-Biomolécules (PCEBM), UFR de Pharmacie Université Joseph Fourier Grenoble I, La Tronche, France.
Ribuot
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Durand
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Demenge
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes / Q000378:metabolism; D020120:Iodocyanopindolol / Q000378:metabolism / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017725:Ventricular Pressure / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D007545:Isoproterenol