title: Role of adrenergic receptor systems in canine left ventricular hypertrophy.
abstract: Although the sympathetic nervous system and catecholamines have been postulated to play an important role in the development of myocardial hypertrophy, the precise mechanism is still ill-defined. We therefore investigated myocardial norepinephrine and the adrenergic receptor systems in two experimental canine models for cardiac hypertrophy; in 12 dogs with surgical cardiac denervation, and in 12 dogs with chronic infusion of a subhypertensive dose of norepinephrine at a rate of 0.04 mg/kg/day. After two months both models induced myocardial hypertrophy, indicated by significant increases in the heart weight, left ventricular wall thickness and cell diameter, as compared with 14 sham-operated control dogs. Cardiac denervation remarkably depleted myocardial norepinephrine while plasma norepinephrine remained unchanged. Both alpha 1- and beta-receptors were up-regulated, with Bmax increasing by 124% and 49%, respectively. The decrease in myocardial cyclic AMP content was relatively small as compared with the marked depletion in myocardial norepinephrine, probably compensated by augmentation of beta-receptor system activity. Chronic norepinephrine infusion also reduced myocardial norepinephrine content possibly due to stimulation of presynaptic alpha 2-receptor inhibiting norepinephrine synthesis and release. The number of alpha 1- and beta-receptors also increased by 97% and 30%, respectively, while myocardial cyclic AMP content remained unchanged. These observations indicate that neither direct stimulation of norepinephrine on the myocardial cell nor increased cyclic AMP is the mechanism for cardiac hypertrophy. A greater increase in the alpha 1-receptor, rather than in the beta-receptors, in both models implies that a disproportional augmentation of the alpha 1-receptor system may play an important role in the development of myocardial hypertrophy.
authors.affiliation: Third Department of Medicine, Kurume University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Shida
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: H
authors.initials: H
authors.lastname: Toshima
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013562:Sympathectomy
chemical_list: D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009638:Norepinephrine