Nitric oxide-mediated vasodilation becomes independent of -adrenergic receptor activation with increased intensity of hypoxic exercise

Casey DP, Curry TB, Wilkins BW, Joyner MJ. Nitric oxidemediated vasodilation becomes independent of -adrenergic receptor activation with increased intensity of hypoxic exercise. J Appl Physiol 110: 687– 694, 2011. First published December 30, 2010; doi:10.1152/japplphysiol.00787.2010.—Hypoxic vasodilation in skeletal muscle at rest is known to include -adrenergic receptorstimulated nitric oxide (NO) release. We previously reported that the augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes -adrenergic mechanisms. However, it is unclear whether a -adrenergic receptor-stimulated NO component exists during hypoxic exercise. We hypothesized that NO-mediated vasodilation becomes independent of -adrenergic receptor activation with increased exercise intensity during hypoxic exercise. Ten subjects (7 men, 3 women; 23 1 yr) breathed hypoxic gas to titrate arterial O2 saturation to 80% while remaining normocapnic. Subjects performed two consecutive bouts of incremental rhythmic forearm exercise (10% and 20% of maximum) with local administration (via a brachial artery catheter) of propranolol ( -adrenergic receptor inhibition) alone and with the combination of propranolol and nitric oxide synthase inhibition [N-monomethyl-L-arginine (L-NMMA)] under normoxic and hypoxic conditions. Forearm blood flow (FBF, ml/min; Doppler ultrasound) and blood pressure [mean arterial pressure (MAP), mmHg; brachial artery catheter] were assessed, and forearm vascular conductance (FVC, ml·min ·100 mmHg ) was calculated (FBF/ MAP). During propranolol alone, the rise in FVC ( from normoxic baseline) due to hypoxic exercise was 217 29 and 415 41 ml·min ·100 mmHg 1 (10% and 20% of maximum, respectively). Combined propranolol-L-NMMA infusion during hypoxic exercise attenuated FVC at 20% (352 44 ml·min ·100 mmHg ; P 0.001) but not at 10% (202 28 ml·min ·100 mmHg ; P 0.08) of maximum compared with propranolol alone. These data, when integrated with earlier findings, demonstrate that NO contributes to the compensatory vasodilation during mild and moderate hypoxic exercise; a -adrenergic receptor-stimulated NO component exists during low-intensity hypoxic exercise. However, the source of the NO becomes less dependent on -adrenergic mechanisms as exercise intensity increases.