ENDOGENOUS BR STIMULATES ISCHEMICALLY SENSITIVE ABDOMINAL VISCERAL C-FIBER AFFERENTS THROUGH KININ B-2-RECEPTORS

Abdominal ischemia and reperfusion reflexly activate the cardiovascula r system. In the present study, we evaluated the role of endogenously produced bradykinin (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of a nesthetized cats during 5 min of abdominal ischemia. Abdominal ischemi a increased the portal venous plasma BK level from 49 +/- 10 to 188 +/ - 66 pg/ml (P < 0.05). Injection of BK (1 mu g/kg ia) into the descend ing aorta significantly increased impulse activity (0.88 +/- 0.16 impu lses/s) of 10 C fibers, whereas a kinin B-1-receptor agonist, des-Arg( 9)-BK (1 mu g/kg), did not alter the discharge rate. Inhibition of kin inase II activity with captopril (4 mg/kg iv) potentiated impulse acti vity of 14 ischemically sensitive C fibers (0.44 +/- 0.09 vs. precapto pril, 0.33 +/- 0.08 impulses/s; P < 0.05). In addition, a kinin B-2-re ceptor antagonist (NPC-17731; 40 mu g/kg iv) attenuated activity of af ferents during ischemia (0.39 +/- 0.08 vs. pre-NPC-17731, 0.72 +/- 0.1 3 impulses/s; P < 0.05) and eliminated the response of 10 C fibers to BK. Another kinin B(2)receptor antagonist, Hoe-140 (30 mu g/kg iv), ha d similar inhibitory effects on six other ischemically sensitive C fib ers. In 15 separate cats treated with aspirin (50 mg/kg iv), Hoe-140 ( 30 mu g/kg iv) attenuated impulse activity of only 3 of 16 ischemicall y sensitive C fibers. These data suggest that BK produced during abdom inal ischemia contributes to the stimulation of ischemically sensitive visceral C fiber afferents through kinin B-2 receptors. Furthermore, the data indicate that for most ischemically sensitive C fibers (81%), BK activates the cyclooxygenase system to augment afferent activity d uring abdominal ischemia.