title: Altered vascular response to acetylcholine in conditions of endothelial damage in the isolated perfused rat stomach.
abstract: To examine the mechanism of stress ulcers and the relation between endothelium derived relaxing factor (EDRF)/NO and gastric mucosal blood flow (GMBF), we used an isolated perfused rat stomach model and studied the effects of an autonomic nerve activator, nitric oxide synthase (NOS) synthesis, and an EDRF/NO inhibitor on gastric blood circulation. Rats were divided into four groups according to pretreatment: (1) control; (2) those given gossypol, a drug provoking endothelial cell damage; (3) those given L-N monomethylarginine (L-NMMA), a specific inhibitor of EDRF/NO; and (4) those subjected to water-immersion stress. Using this model we collected the perfusion fluid from the portal vein at various time points. After administration of acetylcholine, the perfusion flow increased in the control group, but perfusion flow showed no change in the L-NMMA group. On the other hand, the perfusion flow decreased in the gossypol and water-immersion stress groups. The perfusion fluid from the control group contained cGMP, but this substance was absent in the perfusion fluid of the other experimental groups. We considered that increased cGMP in the fluid came from endothelial cells. We presume that the presence of EDRF/NO is essential for the control of GMBF and that from the viewpoint of gastric ulcers, the lack of EDRF/NO may be an important factor in the decrease of GMBF in the early stages of water-immersion stress.
authors.affiliation: Third Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Arakawa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D006072:Gossypol / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000098:blood supply* / Q000187:drug effects; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D013312:Stress, Physiological; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006152:Cyclic GMP; D006072:Gossypol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester