Protective Effect of Dietary Nitrate on Stress-Induced Gastric Mucosal Injury via Enhancing Blood Perfusion in Mongolian Gerbils
Gastric ulceration caused by stress is a significant medical concern, particularly in critically ill patients. Stress-induced ulcers can lead to severe upper gastrointestinal bleeding, which is associated with a high mortality rate. One of the models used to study stress-induced gastric injury is water immersion and restraint stress (WIRS), which combines physical and psychological stressors to mimic the gastric lesions caused by sepsis, trauma, or surgery. Adequate mucosal blood flow is crucial for protecting the gastric mucosa from injuries. Inorganic nitrate, commonly found in vegetables, can be rapidly converted to nitrite by oral bacteria and further reduced to nitric oxide (NO) in the acidic environment of the stomach. Dietary nitrate, serving as a biological reservoir for NO, has shown potential in preventing cardiovascular diseases, vascular damage, and high blood pressure in both animal models and humans. This study explores the role of dietary nitrate in mitigating stress-induced gastric mucosal injury in Mongolian gerbils by enhancing blood perfusion.
The study involved male Mongolian gerbils weighing between 40 to 60 grams, which were randomly divided into three groups: Control (without WIRS), WIRS, and WIRS + nitrate (sodium nitrate). Each group consisted of six animals. The nitrate-treated group received 5 mmol/L sodium nitrate dissolved in distilled water for one week before undergoing WIRS. The daily nitrate intake in this group was approximately 1 mmol/kg. The control and WIRS groups were given distilled water containing sodium chloride at the same dose. The WIRS procedure involved fasting the gerbils for 18 to 20 hours, fixing them on a rat board, and immersing them in water at 20 ± 2°C up to the depth of the xiphoid process for four hours. After general anesthesia, the stomach was removed for analysis.
Gastric mucosal blood flow was measured using laser Doppler flowmetry (LDF) with a vascular monitor system. The mucosal blood flow in the glandular stomach was determined as a voltage output and expressed in perfusion units (PU). An optical probe was placed 0.5 mm above and perpendicular to the mucosal surface, and blood flow was measured at three points, with each measurement lasting three minutes. The average value was calculated for each animal. Statistical analysis was performed using SPSS 17.0 software, with data presented as mean ± standard deviation. Comparisons between groups were made using Student’s t-test, with a P-value of less than 0.05 considered statistically significant.
The results showed that the WIRS group exhibited severe injuries in the glandular stomach, characterized by elongated bands of hemorrhage and tissue edema. In contrast, the nitrate-pretreated group showed a significant reduction in these injuries. The ulcer index in the WIRS group was significantly higher (32.60 ± 7.02) compared to the nitrate-pretreated group (13.40 ± 6.95, P = 0.002). Gastric mucosal blood flow was also significantly decreased in the WIRS group (32.31 ± 17.38 PU) compared to the control group (64.16 ± 16.26 PU, P = 0.017). However, oral administration of nitrate significantly restored gastric mucosal blood flow (58.77 ± 17.51 PU) compared to the WIRS group (P = 0.043).
The gastric mucosa is continuously exposed to various noxious factors, and its defense mechanisms include the production of bicarbonate in surface mucus, regulation of gastric mucosal blood flow, and acceleration of epithelial regeneration. Among these, gastric mucosal blood flow plays a pivotal role in the recovery from injuries. This study demonstrates that dietary nitrate exerts a gastroprotective effect in Mongolian gerbils, likely due to its ability to enhance gastric mucosal blood flow. The findings suggest that nitrate therapy could be a novel preventive strategy against stress-related organ injuries.
The study was supported by a grant from the Natural Science Foundation of Shandong Province (No. ZR2017BH034). The authors declared no conflicts of interest. The findings of this research provide valuable insights into the potential therapeutic benefits of dietary nitrate in protecting against stress-induced gastric mucosal injury, emphasizing the importance of maintaining adequate mucosal blood flow for gastric health.
doi.org/10.1097/CM9.0000000000000943
Was this helpful?
0 / 0