Histamine receptor subtypes mediating hyperpolarization in the isolated, perfused rat mesenteric pre-arteriolar bed.
Histamine is a general dilator of rat blood vessels. We investigated the relative contribution of receptor subtypes to the rat mesenteric dilator responses initiated by histamine and related agonists. Histamine initiated dose, and endothelium-dependent, dilation of constricted mesenteric beds with an ED50 of 0.4 +/- 0.1 nmol. The ED50 was increased 10-fold by 0.1 microM chlorpheniramine (a histamine H1-receptor selective antagonist). Histamine H2 receptor blockade with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a selective histamine H3 receptor antagonist, did not block histamine-induced dilation. Mesenteric bed dilation initiated by histamine H2 receptor selective agonists, amthamine and dimaprit, were antagonized markedly by tiotidine. However, the dilation initiated by the putative histamine H3 receptor selective agonists, R(-)- or S(+)-alpha-methylhistamine and imetit were not affected by thioperamide (1 microM). Histamine H2- and H3-receptor mediated dilator effects were endothelium-independent and were blocked by either excess (80 mM) extracellular K+, or 1 mM tetrabutylammonium (a non-selective K+ channel blocker), as well as by 1 microM dequalinium, a non-peptide blocker of the small conductance Ca2+-activated (SKCa) K+ channels. We conclude that (i) histamine H1 receptor subtype predominantly mediates endothelium-dependent dilator effect of histamine, and (ii) vascular hyperpolarization through opening of K+ channels (SKCa) mediate the dilator responses to histamine H2 receptor (amthamine and dimaprit) and the putative histamine H3 receptor (R(-)-alpha-methylhistamine and imetit) agonists.
Adeagbo
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AS
Department of Physiology and Biophysics, University of Louisville, KY 40292, USA. asadea01@ulkyvm.louisville.edu
Oriowo
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MA
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000502:physiology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011968:Receptors, Histamine; D006632:Histamine; D011188:Potassium