ono-11120 and ozagrel

Topics: Animals; Aspirin; Blood Coagulation Disorders; Cyclooxygenase Inhibitors; Dogs; Fatty Acids, Monounsaturated; Humans; Methacrylates; Phospholipases; Receptors, Prostaglandin; Receptors, Thromboxane; Renal Dialysis; Sulfinpyrazone; Thromboxane A2; Thromboxane-A Synthase

The involvement of a thromboxane (TX) A2-like substance in the decrease of mucosal blood flow (MBF) and occurrence of gastric erosions in rats under water-immersion stress was examined. MBF was estimated by aminopyrine clearance. Stress increased acid output without a parallel increase in MBF and caused erosions. OKY-046, an inhibitor of TXA2 synthesis, and ONO-11120, an antagonist of TXA2 receptors, increased MBF during stress in parallel with an increase in acid output, and erosions did not form. In another experiment, the effects of a TXA2-like substance on MBF during vagal stimulation were examined. Although vagal stimulation alone increased acid output, there were no erosions in the stomach, probably because MBF was increased in parallel with acid output. Intra-arterial administration of a TXA2-like substance formed by the metabolism of arachidonic acid in the blood reduced MBF during vagal stimulation. Intra-arterial administration of ONO-11113, an agonist of TXA2 receptors, also reduced MBF during vagal stimulation. Neither agent affected the elevated level of acid output during vagal stimulation, and erosions formed in the glandular part of the stomach. These results suggested that the gastric mucosal erosions induced by water-immersion stress in rats were due to mucosal ischemia produced by the presumed formation of a TXA2-like substance and to the increased secretion of acid.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Gastric Juice; Gastric Mucosa; Ischemia; Male; Methacrylates; Rats; Receptors, Prostaglandin; Receptors, Thromboxane; Regional Blood Flow; Stomach Ulcer; Stress, Psychological; Thromboxane A2; Vagus Nerve