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Randomized Controlled Trial
. 2013 Nov;76(5):699-707.
doi: 10.1111/bcp.12110.

Histamine-induced vasodilatation in the human forearm vasculature

Euan A Sandilands  1 , Jane Crowe, Hayley Cuthbert, Paul J Jenkins, Neil R Johnston, Michael Eddleston, D Nicholas Bateman, David J Webb
Affiliations
Randomized Controlled Trial

Histamine-induced vasodilatation in the human forearm vasculature

Euan A Sandilands et al. Br J Clin Pharmacol. 2013 Nov.

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.

Keywords: forearm blood flow; histamine; vasodilatation; venous occlusion plethysmography.

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Figures

Figure 1
Figure 1
(A) FBF in response to an i.a. histamine infusion. ▪ infused arm; □ control arm. (B) Flare and itch associated with an i.a. histamine infusion. □ flare; ○ itch
Figure 2
Figure 2
(A) Study of acute tolerance to i.a. histamine. ▪ infused arm; □ control arm. (B) Flare and itch associated with the continuous infusion of i.a. histamine. □ flare; ○ itch
Figure 3
Figure 3
FBF, flare and itch in the presence of histamine and histamine antagonists/placebo. formula image placebo; formula image H1-receptor antagonist; formula image H2-receptor antagonist; formula image H1- and H2-receptor antagonist
See this image and copyright information in PMC

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