Inhibition in the rat of nitric oxide synthesis in vivo does not attenuate the hypotensive action of acetylcholine, ATP or bradykinin.
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.
O'Shaughnessy
K M
KM
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
Newman
C M
CM
Warren
J B
JB
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
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester