Histamine‐induced vasodilatation in the human forearm vasculature

Abstract

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 H2-receptor antagonists. Flare and itch were assessed in all studies. RESULTSHistamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min ; 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. CONCLUSIONHistamine 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.

Histamine H2-receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II–hypertensive mice

“…While most of the classical histamine-dependent effects in allergic reactions are H 1 receptor–mediated [ 54 ], H 2 receptors are involved in the associated vasodilator responses [ 28 , 50 , 54 , 55 ]. Thus, in studies on rat mesenteric arteries and rabbit aortae, histamine-induced dilatations are mediated by H 2 receptors [ 28 , 34 ]; likewise, in humans, relaxations to exogenous histamine of isolated uterine arteries are prevented by H 2 antagonists [ 55 ], as are histamine-induced increases in forearm blood flow [ 50 ]. Histamine-induced NO release in porcine endothelial cells is mediated by H 2 receptors [ 33 ].…”

Ipsilateral somatic nerves mediate histamine-induced vasosensory reflex responses involving perivascular afferents in rat models

“…Earlier studies in dogs and cats have reported that injection of histamine into femoral vein causes a systemic fall in blood pressure as measured from femoral artery 14 – 16 . Further, administration of histamine into brachial vein has shown to produce veno-dilation and increased forearm blood flow in humans 17 . The above works by far, describe the effects of histamine only on BP, due to its presence in the systemic circulation.…”

Untargeted metabolomics for uncovering biological markers of human skeletal muscle ageing

“…The interplay between the two amine pathways is still not fully understood, however histamine may impact expression of the enzyme ornithine decarboxylase (ODC), a key step in polyamine synthesis [ 61 – 63 ]. Histamine is a prominent vasoactive substance, helping regulate blood-flow and vascular tone [ 64 , 65 ]. It is well established that the control of blood flow is impaired in ageing with significant decrease in flow and microvascular perfusion to the muscle in response to nutritive stimuli [ 66 , 67 ].…”