Involvement of perivascular nerves and transient receptor potential vanilloid 1 (TRPV1) in vascular responses to histamine in rat mesenteric resistance arteries

Honghua Jin, Pengyuan Sun, Shingo Takatori, Toshihiro Koyama, Yoshito Zamami, Panot Tangsucharit, Yoshihisa Kitamura, Hiromu Kawasaki

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10 Citations (Scopus)


A previous report showed that histamine in denuded mesenteric vascular beds produced a triphasic response; an initial small histamine H2 receptor-mediated vasodilation, a transient histamine H1 receptor-mediated vasoconstriction, and finally a long-lasting vasodilation. We further investigated the vascular effect of histamine in mesenteric preparations without an endothelium to clarify the possible involvement of perivascular nerves. Male Wistar rat mesenteric vascular beds without an endothelium were perfused with Krebs solution containing methoxamine to produce active tone and lafutidine to block histamine H2 receptor-mediated vasodilation. Histamine (1-100 μM) was perfused for 1 min and perfusion pressure was measured with a pressure transducer. Histamine caused a biphasic vascular response; initial vasoconstriction followed vasodilation. Tetrodotoxin (a neurotoxin, 1 μM) and procaine (a local anesthetic, 100 μM) significantly inhibited the vasoconstriction and vasodilation. Ruthenium red (a transient receptor potential vanilloid 1 (TRPV1) antagonist, 1 μM) also significantly inhibited both phases of the response. Pretreatment with capsaicin (a depletor of calcitonin gene-related peptide (CGRP)-containing nerves, 5 μM) significantly inhibited the vasodilation without affecting the initial vasoconstriction. Both indomethacin (a cyclooxygenase inhibitor, 0.5 μM) and seratrodast (a thromboxane A2 receptor antagonist, 0.1 μM) abolished the histamine-induced vasoconstriction and subsequent vasodilation. These results suggest that histamine-induced vasoconstriction and long-lasting vasodilation are mediated by activation of TRPV1 on capsaicin-sensitive and capsaicin-insensitive nerves. They also suggest that perivascular nerves and prostanoids, probably thromboxane A2, are responsible for the vascular response to histamine.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - Apr 5 2012


  • Histamine
  • Perivascular nerve
  • Rat mesenteric resistance artery
  • Transient receptor potential vanilloid 1
  • Vasoconstriction
  • Vasodilation

ASJC Scopus subject areas

  • Pharmacology


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