title: Local nitric oxide release does not affect tachyphylaxis to angiotensin II in dorsal hand veins in man in the presence of prostaglandin synthesis inhibition.
abstract: OBJECTIVE
  Local prostaglandin (PG) production contributes to tachyphylaxis to angiotensin II (ANGII) in veins. Our aim was to assess the hypothesis that local nitric oxide (NO) generation is also, in part, responsible for tachyphylaxis to ANGII in veins, using the Aellig dorsal hand vein technique.
  
  
  METHODS
  Eight healthy male volunteers received 600 mg of aspirin (orally) to inhibit PG production. The venoconstrictor effects of ANGII and noradrenaline (NA) were then compared in dorsal hand veins during co-infusion of the NO synthase inhibitor L-NMMA or saline, on separate occasions.
  
  
  RESULTS
  ANGII and NA produced a similar degree of initial venoconstriction. However, the response to ANGII was significantly attenuated by 12 min compared with NA (AUC 147 +/- 38 vs 196 +/- 40, respectively; [95% confidence interval for difference: 7, 92], P = 0.02). Infusion of L-NMMA did not influence the response to ANGII or NA (P = 0.2 and P = 0.3, respectively).
  
  
  CONCLUSIONS
  Tachyphylaxis to ANGII in dorsal hand veins is not dependent on local NO release.
authors.affiliation: Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2LH, Scotland, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: de Haas
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: J L
authors.initials: JL
authors.lastname: Boyd
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D016037:Single-Blind Method; D013618:Tachyphylaxis / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001241:Aspirin; D009638:Norepinephrine