title: Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide.
abstract: Although endothelium-derived nitric oxide contributes to basal vascular tone, little is known about its role in regulating blood flow during changes in metabolic supply and demand. We examined the contribution of endothelium-derived nitric oxide to reactive hyperemia in the forearm of 20 normal subjects (12 women, 8 men) aged 27 +/- 4 yr (means +/- SD), using the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). Forearm ischemia was induced by suprasystolic blood pressure cuff inflation for 5 min, and the subsequent hyperemic flow was recorded for 5 min using venous occlusion strain-gauge plethysmography. The efficacy of nitric oxide blockade was tested by comparing the dose-response relationship to the endothelium-dependent agonist, acetylcholine (3, 10, and 30 mg/min), before and after intra-arterial infusion of up to 2,000 mg/min of L-NMMA. L-NMMA produced a significant downward and rightward shift in the dose-response relationship to acetylcholine and a 39% reduction in response to the maximum dose (P < 0.001). In the presence of L-NMMA, peak hyperemic flow was reduced 16% (26.5 +/- 2.1 to 22.3 +/- 1.5 ml.min-1.100 ml of forearm-1, P < 0.03), and the minimum forearm vascular resistance was increased 22.8% (3.5 +/- 0.3 to 4.3 +/- 0.4 mmHg.ml-1.min.100 ml, P < 0.02). Total hyperemia, calculated from the area under the flow vs. time curve, at 1 and 5 min after cuff release was 17 and 23% less, respectively (13.6 +/- 1.2 vs. 11.3 +/- 1.1 and 31.8 +/- 2.7 vs. 24.6 +/- 1.8 ml/100 ml, P < 0.002), following L-NMMA. These data suggest that endothelium-derived nitric oxide plays a role in both reactive hyperemia and in the maintenance of the hyperemic response following ischemia in the forearm.
authors.affiliation: Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: I T
authors.initials: IT
authors.lastname: Meredith
authors.forename: K E
authors.initials: KE
authors.lastname: Currie
authors.forename: T J
authors.initials: TJ
authors.lastname: Anderson
authors.forename: M A
authors.initials: MA
authors.lastname: Roddy
authors.forename: P
authors.initials: P
authors.lastname: Ganz
authors.forename: M A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001810:Blood Volume / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine