Histamine H3 agonist decreases arterial blood pressure in the guinea-pig.
Intravenous injection of an H3-agonist, (R)-alpha-methylhistamine, dose-dependently caused a transient fall in mean arterial pressure of guinea-pigs. This pressor response was not reduced by combined mepyramine/cimetidine (up to 1 mg kg-1), atropine or propranolol, but was attenuated by either a selective H3-antagonist, thioperamide, or a competitive inhibitor of nitric oxide synthesis, NG-monomethyl L-arginine. The reduction by the inhibitor of nitric oxide synthesis was reversed by L- but not D-arginine. Histamine activated the H3-sites since its depressor response (obtained with mepyramine and cimetidine) was similar to that of (R)-alpha-methylhistamine. Our data indicate that H3-sites could exist in the cardiovascular system of guinea-pigs and that their stimulation might be mediated through the L-arginine/nitric oxide pathway.
Kim
L E
LE
Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France.
Javellaud
J
J
Oudart
N
N
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D018100:Receptors, Histamine H3 / Q000187:drug effects*
D017442:Histamine Agonists; D008761:Methylhistamines; D018100:Receptors, Histamine H3; D019335:Nitroarginine; D009569:Nitric Oxide; C069357:alpha-methylhistamine; D006632:Histamine; D001120:Arginine