Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of beta-adrenoceptors.
The present study was undertaken to assess cardiac function and characterize beta-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. beta-Adrenoceptors were assessed using Western blots and [(3)H]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%. beta(1)- and beta(2)-adrenoceptor proteins were reduced by 60% and 40%, respectively, while beta(3)-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [(3)H]dihydroalprenolol, consistent with reductions in beta(1)- and beta(2)-adrenoceptors. Three weeks of ExT initiated 4 wk after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of beta(1)-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in beta(2)-adrenoceptor or the increase of beta(3)-adrenoceptor expression. ExT also increased [(3)H]dihydroalprenolol binding, consistent with increased beta(1)-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily beta(1)-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.
Bidasee
Keshore R
KR
Dept. of Pharmacology and Experimental Neuroscience, Univ. of Nebraska Medical Center, DRC 3047, Omaha, NE 68198-5800, USA. kbidasee@unmc.edu
Zheng
Hong
H
Shao
Chun-Hong
CH
Parbhu
Sheeva K
SK
Rozanski
George J
GJ
Patel
Kaushik P
KP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D004082:Dihydroalprenolol / Q000378:metabolism; D004452:Echocardiography; D005081:Exercise Therapy; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D004082:Dihydroalprenolol; D007545:Isoproterenol