Histamine‐induced vasodilatation in the human forearm vasculature. (21st October 2013)

• Record Type: Journal Article
• Authors: Sandilands, Euan A.; Crowe, Jane; Cuthbert, Hayley; Jenkins, Paul J.; Johnston, Neil R.; Eddleston, Michael; Bateman, D. Nicholas; Webb, David J.
• Is Part Of: British journal of clinical pharmacology. Volume 76:Number 5(2013:Nov.)
• Page Start: 699
• Page End: 707
• Publication Date: 2013-10-21
• Subjects: forearm blood flow -- histamine -- vasodilatation -- venous occlusion plethysmography; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.12110
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : Aim: 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. Conclusion: 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.