AimTo investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature.
MethodsThree 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.
ResultsHistamine caused a dose-dependent increase in FBF, greatest with the highest dose (30nmolmin(-1)) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6mlmin(-1)100ml(-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 30nmolmin(-1) histamine: -11.9mlmin(-1)100ml(-1) (-4.0, -19.8), P <0.0001) and flare (mean (95% CI) difference from placebo: -403.7cm(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 Willebrand factor.
ConclusionHistamine 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.
- forearm blood flow
- venous occlusion plethysmography
- PLASMINOGEN-ACTIVATOR RELEASE
- HUMAN-ENDOTHELIAL CELLS