Cardiovascular/Autonomic Phenotype for db/db Diabetic Mice

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The db/db mice serve as a good model for type 2 diabetes, characterized by hyperinsulinemia and progressive hyperglycemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim was to characterize the cardiovascular/autonomic phenotype of male db/db mice and evaluate the role of angiotensin (Ang) AT1 receptors. Radiotelemetry was used to monitor 24 hr blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. MAP and BP circadian rhythms were not altered in 8 wk db/db while HR and locomotor activity were decreased. With aging, MAP gradually increased in db/db mice and the 12-h light values did not dip significantly from the 12-h dark periods. In 14 wk mice, MAP was increased during light (101 ± 1 vs. 117 ± 2 mmHg, p < 0.01; Control vs. db/db) and dark phases (110 ± 1.7 vs. 121 ± 3.1 mmHg, pdb/db). This increase in BP was associated with significant increase in plasma ACE activity and Ang II levels. Chronic treatment with losartan (10 mg/kg/day) blocked the increase in MAP in db/db with no effect in controls. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in SAP variance and its LF component in control mice was absent in db/db. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db/db mice. Results document an age related increase in MAP in db/db reduced by antagonism of Ang AT1 receptors and alterations in autonomic balance and components of the renin angiotensin system.