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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Vydáno v:	British journal of clinical pharmacology Ročník 76; číslo 5; s. 699 - 707
Hlavní autoři:	Sandilands, Euan A., Crowe, Jane, Cuthbert, Hayley, Jenkins, Paul J., Johnston, Neil R., Eddleston, Michael, Bateman, D. Nicholas, Webb, David J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Blackwell Science Inc 01.11.2013
Témata:	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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0306-5251 1365-2125 1365-2125
DOI:	10.1111/bcp.12110