Abstract 355: Increasing Muscle Mass Improves Vascular Function In Obese Mice

Abstract

Exercise improves endothelial function in obese patients. Salutatory effects of exercise include increases in muscle size and quality, reduction in fat mass and alterations of the plasma milieu. The relationships between these changes and improvements in vascular function are poorly defined. Hypothesis Increasing muscle mass by deletion of muscle growth negative regulator myostatin, improves vascular function in mesenteric arteries from obese db/db mice. Myostatin deletion increased muscle mass in both lean (gastrocnemius 57.93%, gluteus maximus 60.95%, triceps 57.64%) and obese mice (gastrocnemius 79.64%, gluteus maximus 112.32%, triceps 103.61%). Myostatin deletion increased muscle fiber size in lean and obese mice (p< 0.05) but had no significant effects on adipocyte size in obese mice. Fasting glucose, HbA1c and glucose tolerance were improved in obese myostatin null mice. Obese mice demonstrated superoxide-mediated impairment of ACh-induced vasodilation compared to lean mice. Deletion of myostatin in obese mice improved ACh-induced vasodilation in mesenteric arteries without effects in lean mice. This improvement was blunted by L-NAME. PGI 2 and EDHF mediated vasodilation were preserved in obese mice, and unaffected by myostatin deletion. Treatment with sepiapterin (a precursor of the nitric oxide synthase cofactor tetrahydrobiopoterin) restored impairment of vasodilation in obese mice, and this improvement was blocked by L-NAME. Taken together, these data suggested that increasing muscle mass by deletion of myostatin improved NO not PGI 2 or EDHF mediated vasodilation in obese mice.