title: Nitric oxide and reactive hyperemia: role of location and duration of ischemia.
abstract: BACKGROUND
  Ischemia-induced reactive hyperemia (RH) is mediated by various factors including release of nitric oxide (NO). The contribution of NO to RH equals the extent of L-NMMA-dependent reduction of forearm blood flow (FBF). Because the optimal duration and location of ischemia that provokes maximum NO activation is unknown, we analyzed which duration and location stimulates most NO release, aiming at developing a noninvasive tool to measure endothelial integrity by NO synthase activity in humans.
  
  
  METHODS
  FBF was measured by strain gauge plethysmography after ischemia applied at the upper arm and wrist during intra-arterial infusion of L-NMMA or saline. To obtain similar FBF before RH, clamping with sodium nitroprissude was performed. Twenty-eight healthy male volunteers were randomly assigned to two groups (N = 15) undergoing ischemia of 1 and 5 min or 2 and 5 min (N = 13) at both locations.
  
  
  RESULTS
  Peak FBF was not affected by L-NMMA infusion. The change of FBF during L-NMMA expressed as area under the curve (AUC) of the first minute was significantly reduced after 1 (-0.70 +/- 1.63 ml, P < 0.001) and 2 min (1.67 +/- 2.65 ml, P < 0.01) of ischemia applied at wrist level compared to 5 min (7.49 +/- 7.92 ml). Ischemia applied to the upper arm showed no significant differences of FBF after L-NMMA or saline infusion, irrespective of the duration of ischemia.
  
  
  CONCLUSIONS
  Our data indicate that only immediately after ischemia the vasodilatatory response is most NO-dependent. RH as a test of NO activity in the forearm microcirculation should be applied at the wrist and last 1 min.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raff
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Stefan
authors.initials: S
authors.lastname: John
authors.forename: Bernhard M W
authors.initials: BM
authors.lastname: Schmidt
authors.forename: Erwin H
authors.initials: EH
authors.lastname: Fleischmann
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000328:Adult; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014953:Wrist / Q000098:blood supply; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide