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Histamine‐induced vasodilatation in the human forearm vasculature
Author(s) -
Sandilands Euan A.,
Crowe Jane,
Cuthbert Hayley,
Jenkins Paul J.,
Johnston Neil R.,
Eddleston Michael,
Bateman D. Nicholas,
Webb David J.
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12110
Subject(s) - histamine , medicine , placebo , forearm , plethysmograph , endocrinology , crossover study , antagonist , vasodilation , anesthesia , receptor , surgery , pathology , alternative medicine
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 H 1 ‐ and H 2 ‐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. H 2 ‐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 H 1 ‐receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von W illebrand factor. Conclusion Histamine causes dose‐dependent vasodilatation, flare and itch in the human forearm. H 2 ‐receptors are important in this process. Our results support further exploration of combined H 1 ‐ and H 2 ‐receptor antagonist therapy in acute allergic syndromes.