title: Histamine-induced vasodilatation in the human forearm vasculature.
abstract: OBJECTIVE
  To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature.
  
  
  METHODS
  Three studies were conducted to assess changes in forearm blood flow (FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose-response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H1 - and H2 -receptor antagonists. Flare and itch were assessed in all studies.
  
  
  RESULTS
  Histamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min(-1) ) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6 ml min(-1)  100 ml(-1) ; P < 0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H2 -receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30 nmol min(-1) histamine: -11.9 ml min(-1)  100 ml(-1) (-4.0, -19.8), P < 0.0001) and flare (mean (95% CI) difference from placebo: -403.7 cm(2) (-231.4, 576.0), P < 0.0001). No reduction in FBF or flare was observed in response to the H1 -receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor.
  
  
  CONCLUSIONS
  Histamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H2 -receptors are important in this process. Our results support further exploration of combined H1 - and H2 -receptor antagonist therapy in acute allergic syndromes.
authors.affiliation: NPIS (Edinburgh), Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Euan A
authors.initials: EA
authors.lastname: Sandilands
authors.forename: Jane
authors.initials: J
authors.lastname: Crowe
authors.forename: Hayley
authors.initials: H
authors.lastname: Cuthbert
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Jenkins
authors.forename: Neil R
authors.initials: NR
authors.lastname: Johnston
authors.forename: Michael
authors.initials: M
authors.lastname: Eddleston
authors.forename: D Nicholas
authors.initials: DN
authors.lastname: Bateman
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D011537:Pruritus / Q000139:chemically induced; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D017442:Histamine Agonists; D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine
keywords: forearm blood flow; histamine; vasodilatation; venous occlusion plethysmography