Analysis of vasoconstrictor responses to histamine in the hindlimb vascular bed of the rabbit

Hunter C. Champion, Trinity J. Bivalacqua, David G. Lambert, Rasheed A. Abassi, Philip J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Hemodynamic responses to histamine were investigated in the anesthetized rabbit. Intravenous injections of histamine induced dose-dependent decreases in systemic arterial pressure that were blocked by the H1-receptor antagonist pyrilamine but not the H2 antagonist cimetidine. Injections of histamine and the H1 agonist 6-[2-(4-imidazolyl)ethylamine]-N-(4- trifuormethylphenyl)-heptanecardoxamide dimaleate (HTMT) into the hindlimb perfusion circuit increased hindlimb perfusion pressure, whereas the H2 agonist dimaprit decreased perfusion pressure and the H3-receptor agonist R- (-)-α-methylhistamine did not alter perfusion pressure. Pyrilamine reduced hindlimb vasoconstrictor responses to histamine and HTMT but did not alter vasodilator responses to dimaprit. Cimetidine reduced the response to dimaprit but did not alter vasoconstrictor responses to histamine or HTMT. The H3-receptor antagonist thioperamide was without effect on responses to the histamine agonists. These data suggest the presence of H1 and H2 receptors and that histamine for the most part acts by stimulating H1 receptors to produce vasoconstriction in the hindlimb vascular bed of the rabbit. Responses to histamine, HTMT, and norepinephrine were significantly enhanced by a nitric oxide synthase inhibitor at a time when vasodilator responses to dimaprit were unaltered and responses to acetylcholine were significantly reduced. Responses to histamine and the H1 and H2 agonists were not affected by the cyclooxygenase inhibitor meclofenamate or by ATP- sensitive K+ channel, α-adrenergic, or angiotensin AT1 receptor antagonists. The present data suggest that H1 receptors mediate both systemic vasodepressor and hindlimb vasoconstrictor responses to histamine.

Original languageEnglish (US)
Pages (from-to)R1179-R1187
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume277
Issue number4 46-4
DOIs
StatePublished - Oct 1999
Externally publishedYes

Keywords

  • ATP-sensitive K channels
  • Alpha receptors
  • Cyclooxygenase products
  • Differential responses to histamine
  • H receptors
  • Nitric oxide
  • Regional vascular bed

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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