Histamine H1 and H3 vasodilator mechanisms in the guinea pig ileum.
OBJECTIVE
Histamine dilates gastrointestinal blood vessels. Whether this is caused by direct activation of vascular histamine receptors or by activation of enteric neurons is not known. The aim of this study was to determine which of these pathways is activated by histamine and to examine the cellular mechanisms involved.


METHODS
The effects of histamine were studied in in vitro submucosal preparations from the guinea pig ileum using videomicroscopy to monitor changes in submucosal arteriolar diameter.


RESULTS
Histamine caused a tetrodotoxin-insensitive dose-dependent dilation (median effective concentration [EC50], 1 mumol/L), showing direct activation of vascular histamine receptors. The H1 antagonist pyrilamine, but not the H2 blocker ranitidine, competitively inhibited the histamine dilatation. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) inhibited histamine vasodilations by 66%. Indomethacin alone did not alter histamine vasodilations but, when combined with L-NMMA, caused a significantly greater inhibition of the histamine response compared with L-NMMA alone. L-Arginine prevented the actions of L-NMMA. In the presence of both H1 and H2 antagonists, periarteriolar stimulation of sympathetic nerves evoked a tetrodotoxin-sensitive vasoconstriction, which was inhibited by histamine (EC50, 0.8 mumol/L). This histamine action was blocked by the H3 antagonist thioperamide.


CONCLUSIONS
Histamine can produce vasodilation of submucosal arterioles by two distinct mechanisms: activation of vascular H1 receptors resulting in release of nitric oxide from endothelium and activation of H3 receptors on sympathetic nerve terminals resulting in presynaptic inhibition of vasoconstrictor tone.
Beyak
M
M
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Vanner
S
S
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000098:blood supply*; D007213:Indomethacin / Q000494:pharmacology; D009433:Neural Inhibition; D009569:Nitric Oxide / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D009569:Nitric Oxide; D006632:Histamine; D007213:Indomethacin