Impairment of Baroreflex Control of Heart Rate in Conscious OVE26 Diabetic Mice (Type 1)

Abstract

Baroreflex control of heart rate (HR) is impaired in human diabetic mellitus. In this study, we used OVE26 mice as an experimental model to examine the effect of diabetes on the baroreflex control of HR. The beta cells in OVE26 mice were specifically damaged due to a calmodulin transgene regulated by the insulin promoter. The damage of beta cells resulted in a sustained high blood glucose level (over 500 mg/dl) and reduced insulin secretion since 30 days of age. OVE26 diabetic and FVB control mice (5–6 months) were anesthetized and the femoral artery and vein were catheterized. On the second day, reflex‐mediated HR responses to phenylephrine (PE)‐ and sodium nitroprusside (SNP)‐ induced arterial pressure (AP) changes were measured in conscious mice. Compared with FVB, we found in OVE26 mice: 1) mean AP (MAP) and HR were decreased (P <0.01); 2) PE‐induced MAP increases were comparable to those in FVB mice (p>0.05); 3) baroreflex‐mediated bradycardia was attenuated (P < 0.01); 4) SNP‐induced MAP decreases were reduced (p< 0.05); 5) baroreflex‐mediated tachycardia was attenuated (P < 0.01). We conclude that baroreflex control of HR is impaired in OVE26 diabetic mice. Our data provided a platform for the examination of functional changes and structural reorganization of the neural components within the baroreflex arc in OVE26 mice (Gu et al., 2008; Huang et al., 2008; Lin et al., 2008a, b; EB abstracts). NIH R01 HL‐79636.