title: Analysis of vasoconstrictor responses to histamine in the hindlimb vascular bed of the rabbit.
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 H(1)-receptor antagonist pyrilamine but not the H(2) antagonist cimetidine. Injections of histamine and the H(1) agonist 6-[2-(4-imidazolyl)ethylamine]-N-(4-trifuormethylphenyl)-heptan ecardo xamide dimaleate (HTMT) into the hindlimb perfusion circuit increased hindlimb perfusion pressure, whereas the H(2) agonist dimaprit decreased perfusion pressure and the H(3)-receptor agonist R-(-)-alpha-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 H(3)-receptor antagonist thioperamide was without effect on responses to the histamine agonists. These data suggest the presence of H(1) and H(2) receptors and that histamine for the most part acts by stimulating H(1) 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 H(1) and H(2) agonists were not affected by the cyclooxygenase inhibitor meclofenamate or by ATP-sensitive K(+) channel, alpha-adrenergic, or angiotensin AT(1) receptor antagonists. The present data suggest that H(1) receptors mediate both systemic vasodepressor and hindlimb vasoconstrictor responses to histamine.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Champion
authors.forename: T J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: D G
authors.initials: DG
authors.lastname: Lambert
authors.forename: R A
authors.initials: RA
authors.lastname: Abassi
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D006632:Histamine / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011968:Receptors, Histamine / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009025:Morpholines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011968:Receptors, Histamine; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D008469:Meclofenamic Acid; C082658:U 37883A; D006632:Histamine; D000218:Adamantane; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine