title: Cardiovascular autonomic regulation in Non-Obese Diabetic (NOD) mice.
abstract: Non-Obese Diabetic (NOD) mice show profound pathomorphological changes in sympathetic ganglia during the development of type 1 diabetes mellitus. We tested the hypothesis that NOD mice represent an experimental model to investigate cardiovascular changes seen in humans with diabetic autonomic neuropathy. Blood glucose (BG) levels were measured once a week. Diabetes mellitus was diagnosed as BG levels exceeded 250 mg/dl twice. NOD mice that did not become diabetic served as control group. Blood pressure (BP) and heart rate (HR) were monitored by telemetry and baroreflex sensitivity (BRS) was calculated with the sequence method or with cross spectral analysis. The measurements were obtained before onset of diabetes and during the 4th week of diabetes. The onset of diabetes was accompanied by a continuous decline in HR (615+/-14 vs. 498+/-23 bpm), whereas BP values remained stable (108+/-2 vs. 111+/-2 mm Hg). The circadian HR rhythm increased in diabetic NOD mice. BRS was higher in diabetic NOD mice than in controls. Atropine reduced BRS more profoundly in diabetic mice compared to non-diabetic mice. Despite pathomorphological similarities of the diabetic autonomic neuropathy between patients with diabetes and diabetic NOD mice, the changes in blood pressure regulation are different. In conclusion the use of diabetic NOD mice as a functional model for human diabetes may be questioned.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany. vgross@mdc-berlin.de
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Partke
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Andrey C
authors.initials: AC
authors.lastname: da Costa Goncalves
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000209:etiology / Q000503:physiopathology; D021081:Chronobiology Disorders / Q000209:etiology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005728:Ganglia, Sympathetic / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D018727:Muscarinic Antagonists / Q000494:pharmacology; D015203:Reproducibility of Results; D013686:Telemetry
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D018727:Muscarinic Antagonists