title: Depletion of endogenous dopamine stores and shift in beta-adrenoceptor subtypes in cardiac tissue following five weeks of chronic denervation.
abstract: Surgical ablation of extrinsic cardiac nerve fibers results in a chronically denervated state of the left ventricle of the heart. The present study was performed to elucidate the effect of a period of 5 weeks of chronic denervation on cardiac catecholamine levels in general and dopamine in particular. Moreover, the possible effect on cardiac beta-adrenoceptor subtypes was investigated. Experiments were performed on adult dogs. In addition to adrenaline and noradrenaline the tissue levels of dopamine were found to be severely depressed. A significant shift from beta1- to beta2-adrenoceptor subtype was observed, while the total beta-adrenoceptor density remained unaffected. The present findings indicate that catecholamine synthesis in chronically denervated hearts is impaired upstream of dopamine and that a shift in beta-adrenoceptor subtype occurs already within a relatively short period of five weeks of denervation, and suggest that the lack of endogenous catecholamines influence the relative expression levels of the two subtypes of beta-adrenoceptors present in cardiac tissue.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Van der Vusse
authors.forename: M L
authors.initials: ML
authors.lastname: Dubelaar
authors.forename: W A
authors.initials: WA
authors.lastname: Coumans
authors.forename: M
authors.initials: M
authors.lastname: Steinfath
authors.forename: C C
authors.initials: CC
authors.lastname: Smith
authors.forename: A J
authors.initials: AJ
authors.lastname: Drake-Holland
authors.forename: M I
authors.initials: MI
authors.lastname: Noble
mesh_terms: D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000378:metabolism*; D004837:Epinephrine / Q000032:analysis; D005260:Female; D006352:Heart Ventricles / Q000294:innervation / Q000378:metabolism; D008297:Male; D009121:Muscle Denervation; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine