Why does histamine cause vasodilation

PLoS One. Published online Jul 9. Yulia Komarova, Editor. Author information Article notes Copyright and License information Disclaimer. Competing Interests: The authors have declared that no competing interests exist. Received Mar 26; Accepted Jun This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

This article has been cited by other articles in PMC. S2 Fig: Endogenous and exogenous histamine induced ear swelling. Abstract Histamine is a mediator of allergic inflammation released mainly from mast cells. Introduction In allergic inflammation, antigen-stimulated mast cells release a range of mediators that can be subdivided into the preformed mediators, the synthesized lipid mediators, and the cytokines and chemokines.

Materials and Methods Ethics Statement All animal experiments were approved by the institutional animal care and use ethical committees of the University of Tokyo approval no. Reagents The following reagents were obtained from the indicated suppliers: Evans blue, bradykinin, anti-dinitrophenol IgE and L-phenylephrine hydrochloride Sigma-Aldrich, St.

Passive cutaneous anaphylaxis test Passive cutaneous anaphylaxis PCA tests were performed as described previously [ 12 ], with slight modification. Blood flow velocity and volume measurements Blood flow velocity B vel was calculated by measuring the velocity of EGFP-tagged blood cells in the mouse ear vessel. Laser doppler velocimeter measurements After the mice had been anaesthetized, histamine was treated percutaneously.

Measurement of vascular contraction The mouse mesenteric artery was excised and placed in physiological saline solution containing Open in a separate window. Fig 1. H1 receptor activation increased vascular permeability.

Two types of vasculature are in mouse ear Whole-mount immunostaining revealed two types of vasculature in the mouse ear Fig 2A. Fig 2. Two types of vasculature are in mouse ear. Histamine increased vascular diameter and blood flow volume via H1 receptor activation We next observed the local vascular dynamics in the ear using in vivo imaging.

Fig 3. Histamine increased blood flow volume. Histamine-induced NO-dependent vascular relaxation increased vascular permeability We next examined the effects of histamine on vascular relaxation and contraction using an isolated rat mesenteric artery preparation. Fig 4. L-NAME or phenylephrine pretreatment inhibited histamine-induced hyperpermeability and vascular relaxation. Histamine disrupted the endothelial barrier in vivo We next assessed the effect of histamine on endothelial barrier formation by observing intercellular adherens junctions.

Fig 5. Histamine regulated endothelial barrier function in vivo. Histamine regulated endothelial barrier function in vitro Endothelial barrier function was evaluated in vitro assay by measuring TER. Fig 6. Histamine regulated endothelial barrier function in vitro. Discussion During allergic inflammation, activated mast cells release a large amount of histamine, leading to vascular hyperpermeability [ 15 , 16 ].

TIF Click here for additional data file. S2 Fig Endogenous and exogenous histamine induced ear swelling. Data Availability All relevant data are within the paper and its Supporting Information files. References 1. Vascular permeability modulation at the cell, microvessel, or whole organ level: towards closing gaps in our knowledge. Cardiovasc Res. Nathan RA. The pathophysiology, clinical impact, and management of nasal congestion in allergic rhinitis.

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Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo. Nature communications. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: role of occludin in endothelial solute barriers.

Bradykinin- and thrombin-induced increases in endothelial permeability occur independently of phospholipase C but require protein kinase C activation. J Cell Physiol. Role of CPI in the regulation of endothelial cytoskeleton. American journal of physiology Lung cellular and molecular physiology. Platelet activating factor modulates microvascular permeability through nitric oxide synthesis. Mol Cell. H1R receptors in the brain can be assessed with PET using [ 11 C]doxepin and [ 11 C]pyrilamine, from which [ 11 C]doxepin provides better image contrast and has lower radiometabolism Funke et al.

Age correlates with H1R density Yanai et al. These imaging results are supported by post-mortem studies. H2R density is not reduced in AD patients Perry et al. Schizophrenic patients have lower binding potential in the frontal and prefrontal cortex and in cingulate gyrus Iwabuchi et al.

Binding potential of [ 11 C]doxepin is significantly higher than that in male subjects in amygdala, hippocampus, medial prefrontal cortex, orbitofrontal cortex, and temporal cortex Yoshizawa et al. Women with anorexia nervosa have higher BP in the amygdala and lentiform nucleus than control female subjects Yoshizawa et al. Histamine H2 receptor H2R is ubiquitously expressed in various tissues, including the stomach , heart, and the brain.

Gastric enterochromaffin-like cells respond to stimulation by gastrin and acetylcholine by releasing histamine, which binds to H2R on parietal cells of the stomach, inducing production of gastric acid; therefore H2R antagonists have been used to treat gastroesophageal reflux disease.

H2R participates in regulation of food intake and glucose metabolism. H2R is involved in regulation of immune responses. In the brain , H2R modulates circadian rhythm and cognitive processes. In the heart , histamine produces a positive inotropic effect via H2Rs in the atrial and ventricular muscles. Both H1Rs and H2Rs are present in the smooth muscle of blood vessels, and activation of those by histamine causes vasoconstriction or vasodilation, respectively. Histamine H3 receptor H3R is mainly expressed on neurons, as presynaptic auto- and heteroreceptor.

H3R density is highest in the posterior hypothalamus where the histaminergic neuron cell bodies are located. H3R inhibits the release of histamine, acetylcholine, noradrenaline, dopamine , and glutamate. Postsynaptic H3R expression may also be involved in regulation of signalling by other neurotransmitters. H3R inhibits the release of norepinephrine from sympathetic nerve terminals.

These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H 1 receptors and endothelium-independent vasodilation via smooth muscle histamine H 2 receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H 1 receptors and perivascular nerves. Abstract The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone.