Metabolic Role of eNOS in Exercising C57/BL6 Mice
Abstract Number: 1001-P
Authors: ROBERT S. LEE-YOUNG, KELLY A. POSEY, DEANNA P. BRACY, FREJYA D. JAMES, JULIO E. AYALA, DAVID H. WASSERMAN.
Institutions: Nashville, TN.
Results: Endothelial nitric oxide synthase (eNOS) is expressed within the vasculature and skeletal muscle of mice, however the importance of eNOS during exercise has yet to be fully assessed in vivo. We examined metabolic alterations during exercise in full (-/-) or partial (+/-) eNOS knockout mice compared to wildtype (WT) littermates. Five days prior to the experiment, catheters were implanted into the carotid artery and jugular vein for sampling and infusions. After 5 days, 5h-fasted mice performed a maximum of 30 min of treadmill exercise at 16m/min. eNOS-/- mice had a reduced exercise capacity (P<0.01) compared to eNOS+/- and WT. At 5 min, 2-[14C]-deoxyglucose and [3H]-bromopalmitic acid were injected for determination of tissue-specific glucose (Kg) and long chain fatty acid (LCFA; Kf) clearance. Plasma insulin and free fatty acid levels were similar between genotypes at rest, as were changes during exercise. Fasting glucose levels did not differ between genotypes, however a marked genotype-dependent response was observed during exercise (see Figure). This difference was not associated with alterations in skeletal muscle Kg, or skeletal muscle and liver glycogen breakdown, all of which were similar between genotypes. In skeletal and cardiac muscle of eNOS-/- mice, Kf was significantly elevated (>2-fold) in response to exercise compared to eNOS+/- and WT (P<0.001). In conclusion, eNOS a) is a major determinant of exercise capacity, b) directly regulates the maintenance of arterial glucose levels in a dose-dependent manner, c) is not associated with muscle glucose clearance or muscle and liver glycogenolysis, and d) increases LCFA clearance in skeletal and cardiac muscle, in what may be a compensation for a decline in glucose.[figure1]
Category: Exercise - Animal