Regeneration and revascularization of a nerve-intact skeletal muscle graft in the spontaneously hypertensive rat

Skeletal muscles in hypertensive subjects develop an increased resistance to insulin that reduces their ability to incorporate glucose and synthesize glycogen. Insulin is an anabolic hormone in muscle, and muscle insulin receptors bind the growth factor, insulin-like growth factor I (IGF-I), an important contributor to muscle development and regeneration. An increase in insulin resistance in hypertensive subjects might produce muscle atrophy and weakness or limit regenerative growth after injury. Regenerative muscle growth was assessed in 24-to 26-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats by subjecting extensor digitorum longus (EDL), an ankle flexor, to a nerve-intact graft procedure. The procedure produces extensive muscle fiber and capillary degeneration, but has little effect on the muscle nerve. Muscle morphology and contractile function were examined in intact and regenerating EDL at 21, 42, and 63 days postgraft. Muscle revascularization was assessed histologically at the same time points. Severe established hypertension did not prevent the reestablishment of a structurally normal capillary network in injured muscles. SHR muscle fiber regeneration and maturation, however, were significantly depressed compared 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 reflect a reduced anabolic response to insulin or IGF-I.