title: Inhibition in the rat of nitric oxide synthesis in vivo does not attenuate the hypotensive action of acetylcholine, ATP or bradykinin.
abstract: The hypotensive action of acetylcholine in vivo may be dependent on the release of the novel vasorelaxant, endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), by the vascular endothelium. However, using two different inhibitors of NO synthesis, NG-monomethyl-L-arginine (L-NMMA, 100 mg/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg), we have been unable to attenuate the hypotensive action of intravenous (i.v.) boluses of acetylcholine in anesthetized rats. L-NMMA also failed to alter the hypotensive effect of i.v. bradykinin and adenosine triphosphate (ATP). NO generation by a column of cultured endothelial cells was, however, completely abolished by L-NMMA. The hypotensive effect of acetylcholine was not affected by glibenclamide at a dose which blocks the effect of i.v. cromakalim, a drug which opens ATP-sensitive K+ channels. The rapid hypotensive response to i.v. bolus acetylcholine, ATP and bradykinin remains unexplained.
authors.affiliation: Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
authors.forename: K M
authors.initials: KM
authors.lastname: O'Shaughnessy
authors.forename: C M
authors.initials: CM
authors.lastname: Newman
authors.forename: J B
authors.initials: JB
authors.lastname: Warren
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D007022:Hypotension / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester