title: Beta-adrenergic neuroeffector mechanisms in cardiac hypertrophy of renin transgenic rats.
abstract: We studied neuroeffector defects in hypertrophied myocardium of hypertensive transgenic rats harboring the mouse Ren-2d gene. In transgenic rats, epinephrine and neuropeptide Y concentrations were reduced. A heterologous desensitization of adenylyl cyclase was observed, which was accompanied by a downregulation of beta 1-adrenergic receptors, an increase of inhibitory G protein alpha-subunits, and a mildly depressed catalyst activity of adenylyl cyclase, whereas the bioactivity of stimulatory G protein alpha-subunits and beta 2-adrenergic receptors was unchanged. Desensitization of adenylyl cyclase was accompanied by a reduced positive inotropic response to isoproterenol, whereas the effect of Ca2+ was unchanged. We conclude that sympathetic neuroeffector defects occur in transgenic rats similar to those observed in human failing myocardium. These alterations occur in the stage of hypertrophy and could contribute to contractile dysfunction in later stages.
authors.affiliation: Klinik III für Innere Medizin, Universität zu Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: M
authors.initials: M
authors.lastname: Moll
authors.forename: B
authors.initials: B
authors.lastname: Schmid
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: M
authors.initials: M
authors.lastname: Castellano
authors.forename: E
authors.initials: E
authors.lastname: Erdmann
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000145:classification / Q000502:physiology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009451:Neuroeffector Junction / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012083:Renin / Q000235:genetics*
chemical_list: D009478:Neuropeptide Y; D011943:Receptors, Adrenergic, beta; D012083:Renin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D009638:Norepinephrine