REGENERATION AND REVASCULARIZATION OF A NERVE-INTACT SKELETAL-MUSCLE GRAFT IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Skeletal muscles in hypertensive subjects develop an increased resista nce to insulin that reduces their ability to incorporate glucose and s ynthesize glycogen. Insulin is an anabolic hormone in muscle, and musc le insulin receptors bind the growth factor, insulin-like growth facto r I (IGF-I), an important contributor to muscle development and regene ration. An increase in insulin resistance in hypertensive subjects mig ht produce muscle atrophy and weakness or limit regenerative growth af ter injury. Regenerative muscle growth was assessed in 24- to 26-wk-ol d spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats by subjecting extensor digitorum longus (EDL), an ankle flexor, to a ner ve-intact graft procedure. The procedure produces extensive muscle fib er and capillary degeneration, but has little effect on the muscle ner ve. Muscle morphology and contractile function were examined in intact and regenerating EDL at 21, 42, and 63 days postgraft. Muscle revascu larization was assessed histologically at the same time points. Severe established hypertension did not prevent the reestablishment of a str ucturally normal capillary network in injured muscles. SHR muscle fibe r regeneration and maturation, however, were significantly depressed c ompared with WKY grafts. The reduced regenerative recovery of SHR EDL in adult animals with severe hypertension does not appear to be due to a failure to restore the muscle nerve or capillary network, but may r eflect a reduced anabolic response to insulin or IGF-I.