Journal Article

Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

Omori, Keisuke, Hori, Masatoshi, Ozaki, Hiroshi, Tsubosaka, Yoshiki, Murata, Takahisa, Kobayashi, Koji, Ashina, Kohei, Nakamura, Tatsuro

2015

Overview

Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Anaphylaxis / Animals / Blood / Blood flow / Blood Flow Velocity - drug effects / Blood Vessels - drug effects / Blood Vessels - metabolism / Blood Vessels - physiology / Cadherin / Cadherins / Capillary Permeability - drug effects / Cells, Cultured / Degranulation / Disruption / Ear, External - blood supply / Ear, External - drug effects / Ear, External - pathology / Endothelial cells / Endothelial Cells - drug effects / Endothelial Cells - metabolism / Endothelium / Endothelium, Vascular - drug effects / Endothelium, Vascular - metabolism / Enzyme Inhibitors - pharmacology / Female / Flow / Histamine / Histamine - metabolism / Histamine - pharmacology / Histamine Agonists - pharmacology / Hostages / Humans / Hypersensitivity / Inflammation / Inhibition / Kinases / Life sciences / Localization / Male / Mast cells / Mice / Microscopy, Fluorescence / Microvasculature / NG-Nitroarginine methyl ester / NG-Nitroarginine Methyl Ester - pharmacology / Nitric oxide / Nitric Oxide Synthase - antagonists & inhibitors / Nitric Oxide Synthase - metabolism / Nitric-oxide synthase / Permeability / Pharmacology / Phenylephrine / Phenylephrine - pharmacology / Physiology / Protein kinase C / Protein Kinase C - metabolism / Proteins / Pyridines - pharmacology / Receptors, Histamine H1 - metabolism / Regulators / rho-Associated Kinases - metabolism / Rocks / Skin / Smooth muscle / Studies / Vascular endothelial growth factor / Vasoconstriction / Vasoconstrictor Agents - pharmacology / Vasodilation - drug effects / Veins & arteries