Effects of activated granulocytes and O2- on microcirculatory injury in acute gastric mucosal lesion in rats induced by sodium cinchophen.

The contribution of granulocytes and their byproducts to acute gastric mucosal lesion (AGML) is unclear. Our previous study showed that granulocytes produced O2- in the gastric mucosa of rats treated with 300 mg/kg of cinchophen (cinchophen ulcer, CU) and in rats subjected to 30 min-ischemia-reperfusion (IR). The present study investigated the effects of granulocytes and O2- on microcirculatory injury (MCI) in the gastric mucosa in both models. To evaluate MCI, we measured the amount of extravasated Evans blue, and monitored changes in blood flow and the formation of vascular casts in the gastric mucosa of rats with and without leukopenia. Mucosal levels of interleukin-8 (IL-8) were also measured, to determine granulocyte migration into the stomach. Our findings were: (1) IL-8 was decreased 30-45 min after CU injection (C-I) or after the start of occlusion (S-O), and levels had increased 90 min after either treatment. (2) Evans blue increased 120-150 min after C-I or S-O. These increases were lower in leukopenic than in non-leukopenic rats. (3) The blood flow decreased after C-I or reperfusion and continued at the same level during the 180-min measurement period. In CU leukopenic rats, the blood flow decreased slowly and was restored gradually. In IR leukopenic rats, the blood flow did not decrease. (4) There was a partial lack of capillary network, narrowing of capillaries, and extravasation of resin 90-120 min after C-I and S-O, and the disturbances were reduced in leukopenic rats in both models. (5) The extravasation of resin was reduced by the administration of superoxide dismutase (SOD) at the time O2- from granulocytes was being produced. (6) These reductions in the extravasation of resin due to leukopenia or SOD were smaller in CU than in IR rats. These findings indicate that granulocytes and O2- contribute to some extent to the MCI in CU rats.