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.

Risk Factors for Gastrointestinal Complications in Aspirin Users: Review of Clinical and Experimental Data

“…Indeed, in a vasodilatory dose, i.g. nitroglycerin protects against acidified aspirin-induced gastric mucosal injury in mice [88]. One recent study demonstrated that aspirin enhance the recurrence of gastric ulcer induced by acetic acid [89], suggesting that the acetic acid gastric ulcer model is suitable for assessing the effect of nitroglycerin on the enhancement of ulcer recurrence by aspirin.…”

Pilot Studies to Demonstrate That Intestinal Mucosal Afferent Nerves Are Functionally Linked to Visceral Adipose Tissue

“…This suggests that calibration of laser Doppler flowmeter in absolute units of blood flow may not be necessary inasmuch as significant hypotheses can be tested by determining relative or directional changes in blood flow. The use of normalized laser Doppler flowmetry values is an acceptable way of handling the data and has yielded meaningful conclusions in a number of physiological and pathophysiological studies in the gut [6,7,14,15,[30][31][32][33] and adipose tissue [34,35]. The laser Doppler flowmetry method can demonstrate the instantaneous onset of changes (increase or decrease) in the tissue under study.…”

Involvement of α2-Adrenoceptors in the Gastric Protective Effect of Nitroglycerin Against Acidified Ethanol-Induced Mucosal Injury

“…The number of mucosal lesions was counted. The length of each lesion was measured by a caliper and summed to give the total length of mucosal lesions for each stomach [13,14].…”

“…In a previous study we reported that intragastric nitroglycerin (5 mg/kg) increased gastric blood flow [14]. The intragastric gavage cannula for the mice was prepared by cutting the sharp tip of an 18-gauge Cathlon IV needle (Critikon, Tampa, FL).…”

“…A previous study reported that intragastric nitroglycerin increased the gastric volume by 1 ml/kg [14]. At time 0, one group of fasted conscious mice received intragastric nitroglycerin (5 mg/kg, 1 ml/kg; n = 8), and two groups (n = 8 each) received intragastric vehicle (1 ml/kg).…”