Role of Adenosine and Nitric Oxide in the Hyperemic Response to Superficial and Deep Gastric Mucosal Injury and H⁺ Back-Diffusion in Cats

Abstract

Background: This study was undertaken to examine the role of adenosine and nitric oxide (NO) in the hyperemic response to H⁺ back-diffusion into superficially or deeply injured gastric mucosa, and the role of adenosine in mucosa when blood flow was reduced with indomethacin. Methods: Cat stomachs were exposed to 2 M NaCl for 10 min followed by luminal perfusion at pH 1. Gastric mucosal blood flow was determined by radioactive microspheres, portal vein blood flow by transit-time flowmetry, and H⁺ backdiffusion/secretion by pH-stat titration, and concentrations of histamine in aortic and portal vein blood were measured. Results: In the antrum pretreatment with the adenosine blocker 8-phenyltheophylline (8-PT) or with N^G-methyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, had no effect on the hyperemic response or mucosal injury. However, pretreatment with 8-PT in addition to indomethacin produced extensive deep lesions in the antrum. In the corpus/fundus 8-PT had no effect on the hyperemic response and did not increase indomethacin-induced lesions. L-NMMA significantly reduced the hyperemic response in corpus/fundus. In areas with deep lesions very high blood flow was observed in the vital part of the mucosa below the necrotic tissue. This hyperemia was reduced by L-NMMA but not by 8-PT. Indomethacin increased the release of histamine during base-line conditions, whereas 8-PT reduced histamine release after damage. Conclusions: This study indicates that usually adenosine is not involved in the hyperemic response to mucosal damage, but it appears to have important protective functions in the antral mucosa under marginal circulatory conditions. NO is one of the mediators of the hyperemic response to mucosal injury in the corpus/fundus.

Key Words:

• Adenosine
• gastric mucosal blood flow
• histamine
• hyperemic response
• mucosal damage
• nitric oxide