title: Nitric oxide-mediated vasodilation becomes independent of beta-adrenergic receptor activation with increased intensity of hypoxic exercise.
abstract: Hypoxic vasodilation in skeletal muscle at rest is known to include β-adrenergic receptor-stimulated nitric oxide (NO) release. We previously reported that the augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes β-adrenergic mechanisms. However, it is unclear whether a β-adrenergic receptor-stimulated NO component exists during hypoxic exercise. We hypothesized that NO-mediated vasodilation becomes independent of β-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 O(2) 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 (β-adrenergic receptor inhibition) alone and with the combination of propranolol and nitric oxide synthase inhibition [N(G)-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(-1)·100 mmHg(-1)) was calculated (FBF/MAP). During propranolol alone, the rise in FVC (Δ from normoxic baseline) due to hypoxic exercise was 217 ± 29 and 415 ± 41 ml·min(-1)·100 mmHg(-1) (10% and 20% of maximum, respectively). Combined propranolol-l-NMMA infusion during hypoxic exercise attenuated ΔFVC at 20% (352 ± 44 ml·min(-1)·100 mmHg(-1); P < 0.001) but not at 10% (202 ± 28 ml·min(-1)·100 mmHg(-1); 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 β-adrenergic receptor-stimulated NO component exists during low-intensity hypoxic exercise. However, the source of the NO becomes less dependent on β-adrenergic mechanisms as exercise intensity increases.
authors.affiliation: Dept. of Anesthesiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. casey.darren@mayo.edu
authors.forename: Darren P
authors.initials: DP
authors.lastname: Casey
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Curry
authors.forename: Brad W
authors.initials: BW
authors.lastname: Wilkins
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D005082:Physical Exertion; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014664:Vasodilation; D055815:Young Adult
chemical_list: D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide