Contribution of nitric oxide to brachial artery vasodilation during progressive handgrip exercise in the elderly.
The reduction in nitric oxide (NO)-mediated vascular function with age has largely been determined by flow-mediated dilation (FMD). However, in light of recent uncertainty surrounding the NO dependency of FMD and the recognition that brachial artery (BA) vasodilation during handgrip exercise is predominantly NO-mediated in the young, we sought to determine the contribution of NO to BA vasodilation in the elderly using the handgrip paradigm. BA vasodilation during progressive dynamic (1 Hz) handgrip exercise performed at 3, 6, 9, and 12 kg was assessed with and without NO synthase (NOS) inhibition [intra-arterial N(G)-monomethyl-l-arginine (l-NMMA)] in seven healthy older subjects (69 ± 2 yr). Handgrip exercise in the control condition evoked significant BA vasodilation at 6 (4.7 ± 1.4%), 9 (6.5 ± 2.2%), and 12 kg (9.5 ± 2.7%). NOS inhibition attenuated BA vasodilation, as the first measurable increase in BA diameter did not occur until 9 kg (4.0 ± 1.8%), and the change in BA diameter at 12 kg was reduced by ∼30% (5.1 ± 2.2%), with unaltered shear rate (


METHODS
407 ± 57, l-NMMA: 427 ± 67 s(-1)). Although shifted downward, the slope of the relationship between BA diameter and shear rate during handgrip exercise was unchanged (


METHODS
0.0013 ± 0.0004, l-NMMA: 0.0011 ± 0.007, P = 0.6) as a consequence of NOS inhibition. Thus, progressive handgrip exercise in the elderly evokes a robust BA vasodilation, the magnitude of which was only minimally attenuated following NOS inhibition. This modest contribution of NO to BA vasodilation in the elderly supports the use of the handgrip exercise paradigm to assess NO-dependent vasodilation across the life span.
Geriatric Research, Education, and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, Utah;
Joel D
JD
Trinity
D Walter
DW
Wray
Melissa A H
MA
Witman
Gwenael
G
Layec
Zachary
Z
Barrett-O'Keefe
Stephen J
SJ
Ives
Jamie D
JD
Conklin
Van
V
Reese
Russell S
RS
Richardson
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
endothelium; nitric oxide; vascular function