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Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors

Departments of ¹Pharmacology and Experimental Neuroscience and ²Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska

Submitted 30 January 2008 ; accepted in final form 24 June 2008

The present study was undertaken to assess cardiac function and characterize β-adrenoceptor subtypes in hearts of diabetic rats that underwent exercise training (ExT) after the onset of diabetes. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. Four weeks after induction, rats were randomly divided into two groups. One group was exercised trained for 3 wk while the other group remained sedentary. At the end of the protocol, cardiac parameters were assessed using M-mode echocardiography. A Millar catheter was also used to assess left ventricular hemodynamics with and without isoproterenol stimulation. β-Adrenoceptors were assessed using Western blots and [³H]dihydroalprenolol binding. After 7 wk of diabetes, heart rate decreased by 21%, fractional shortening by 20%, ejection fraction by 9%, and basal and isoproterenol-induced dP/dt by 35%. β₁- and β₂-adrenoceptor proteins were reduced by 60% and 40%, respectively, while β₃-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [³H]dihydroalprenolol, consistent with reductions in β₁- and β₂-adrenoceptors. Three weeks of ExT initiated 4 wk after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of β₁-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in β₂-adrenoceptor or the increase of β₃-adrenoceptor expression. ExT also increased [³H]dihydroalprenolol binding, consistent with increased β₁-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily β₁-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.

rats; heart; streptozotocin; contractility; isoproterenol