title: Intragastric nitroglycerin at a vasodilatory dose attenuates acidified aspirin-induced gastric mucosal injury.
abstract: Clinical studies reveal that aspirin intake to prevent myocardial and cerebral ischemia is associated with a significant increase in upper gastrointestinal hemorrhage requiring hospitalization and that nitroglycerin or long-acting nitrates significantly lower this risk. Nitroglycerin can increase gastric blood flow and slow gastric emptying. We hypothesized that both features contribute to its gastroprotective property. Fasted anesthetized rats (Study 1) and conscious mice (Studies 2 to 4) received intragastric nitroglycerin or vehicle. The effects of these two treatments on various parameters were assessed in Study 1, on blood pressure and gastric blood flow; Study 2, on acidified aspirin-induced gastric mucosal lesions; and Study 3, on the weight of gastric content. In Study 4, the effect of nitroglycerin, vehicle, or vehicle plus saline, on acidified aspirin-induced gastric mucosal lesion was assessed. Compared with vehicle, nitroglycerin decreased blood pressure and produced a mild but significant increase in gastric vascular conductance, blood flow, and volume of gastric content. The number and length of gastric mucosal lesions induced by acidified aspirin were significantly attenuated by intragastric nitroglycerin in a vasodilatory dose. Exogenous saline in a volume equivalent to the increase produced by nitroglycerin, however, did not attenuate the lesions. These experimental data are consistent with the clinical observation that nitrates lower the risk of aspirin-induced gastrointestinal complications. Confirmation of the efficacy of nitroglycerin and nitrates in preventing such aspirin-induced complications in controlled trials is worthy of consideration by clinical investigators.
authors.affiliation: Research and Medical Services, Sepulveda Ambulatory Care Center, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, Los Angeles, California 91343, USA. felix.leung@med.va.gov
authors.forename: Felix W
authors.initials: FW
authors.lastname: Leung
authors.forename: Chi Chung
authors.initials: CC
authors.lastname: Chan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001241:Aspirin / Q000633:toxicity; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D005996:Nitroglycerin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014665:Vasodilator Agents; D005996:Nitroglycerin; D001241:Aspirin