title: Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.
abstract: Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart.
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: H P Aye
authors.initials: HP
authors.lastname: Thaung
authors.affiliation: Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: J Chris
authors.initials: JC
authors.lastname: Baldi
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Wang
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Gillian
authors.initials: G
authors.lastname: Hughes
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Rosalind F
authors.initials: RF
authors.lastname: Cook
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Carol T
authors.initials: CT
authors.lastname: Bussey
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Phil W
authors.initials: PW
authors.lastname: Sheard
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bahn
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Jones
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Schwenke
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand regis.lamberts@otago.ac.nz.
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013233:Stellate Ganglion / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D011943:Receptors, Adrenergic, beta