The Effects Of Voluntary Exercise And Prazosin On Capillary Rarefaction And Metabolism In Streptozotocin-Induced Diabetic Male Rats

Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C: F) in streptozotocin (STZ)-treated diabetic rats. STZ (65 mg/kg) was intraperitoneally administered to male Sprague-Dawley rats (n = 36) to induce diabetes, with healthy, nondiabetic, sedentary rats (n = 10) as controls. The STZ-treated rats were then divided into sedentary (SED) or exercising (EX; 24-h access to running wheels) groups and then further subdivided into prazosin (Praz) or water (H2O) treatment groups: nondiabetic-SED-H2O, STZ-SED-H2O, STZ-EX-H2O, STZSED-Praz, and STZ-EX-Praz. After 3 wk, untreated diabetes significantly reduced the C: F in tibialis anterior (TA) and soleus muscles in the STZ-SED-H2O animals (both P = 0.05). Voluntary exercise and prazosin treatment independently resulted in a normalization of C: F within the TA (1.86 +/- 0.12 and 2.04 +/- 0.03 vs 1.71 +/- 0.09, P +/- 0.05) and the soleus (2.36 +/- 0.07 and 2.68 +/- 0.14 vs 2.13 +/- 0.12, P +/- 0.05). The combined STZ-EX-Praz group resulted in the highest C: F within the TA (2.26 +/- 0.07,P +/- 0.05). Voluntary exercise volume was negatively correlated with fed blood glucose levels (r(2) = -0.7015, P < 0.01) and, when combined with prazosin, caused further enhanced nonfasted glucose (P =0.01). Exercise and prazosin reduced circulating nonesterified fatty acids more than either stimulus alone (P < 0.05). These results suggest that the distinct stimulation of angiogenesis, with both regular exercise and prazosin treatment, causes a cooperative improvement in the microvascular complications associated with T1D. NEW & NOTEWORTHY It is currently well established that poorly controlled diabetes reduces both skeletal muscle mass and muscle capillarization. These muscle-specific features of diabetes may, in turn, compromise insulin sensitivity and glucose control. Using a model of streptozotocin-induced diabetes, we show the vascular complications linked with disease and how chronic exposure to exercise and prazosin (an = 1-adrenergic antagonist) can reduce these complications and improve glycemic control.