title: Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans.
abstract: In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 ± 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4, 8, 12, 16, 20, and 24 kg) with and without endothelial NO synthase blockade [intra-arterial N(G)-monomethyl-L-arginine (L-NMMA), 0.48 mg · dl(-1) · min(-1)]. Higher exercise intensities evoked significant BA vasodilation (4-12%) that was positively correlated with the hyperemic stimulus (r = 0.98 ± 0.003, slope = 0.005 ± 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ∼70% despite similar exercise-induced increases in shear rate (control, +224 ± 30 s(-1); L-NMMA, +259 ± 46 s(-1)). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced (r = 0.48 ± 0.1, slope = 0.0007 ± 0.0005). We conclude that endothelial NO synthase inhibition with L-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans.
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84148, USA. walter.wray@hsc.utah.edu
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Melissa A H
authors.initials: MA
authors.lastname: Witman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: John
authors.initials: J
authors.lastname: McDaniel
authors.forename: Anette S
authors.initials: AS
authors.lastname: Fjeldstad
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Conklin
authors.forename: Mark A
authors.initials: MA
authors.lastname: Supiano
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006225:Hand / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000502:physiology*; D018737:Hand Strength / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000502:physiology
chemical_list: D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase