Histamine‐induced vasodilatation in the human forearm vasculature

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 inv...

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Veröffentlicht in:British journal of clinical pharmacology Jg. 76; H. 5; S. 699 - 707
Hauptverfasser: Sandilands, Euan A., Crowe, Jane, Cuthbert, Hayley, Jenkins, Paul J., Johnston, Neil R., Eddleston, Michael, Bateman, D. Nicholas, Webb, David J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Blackwell Science Inc 01.11.2013
Schlagworte:
Adult
Clinical Trials
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Forearm - blood supply
forearm blood flow
histamine
Histamine - administration & dosage
Histamine - pharmacology
Histamine Agonists - pharmacology
Histamine Antagonists - pharmacology
Humans
Infusions, Intra-Arterial
Male
Middle Aged
Plethysmography
Pruritus - chemically induced
Receptors, Histamine H1 - metabolism
Receptors, Histamine H2 - metabolism
Regional Blood Flow - drug effects
vasodilatation
Vasodilation - drug effects
venous occlusion plethysmography
Young Adult
vasodilatation
histamine
venous occlusion plethysmography
forearm blood flow
ISSN:0306-5251, 1365-2125, 1365-2125
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Zusammenfassung: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 cm2 (−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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0306-5251
1365-2125
1365-2125
DOI:10.1111/bcp.12110