Activation of visceral afferents by bradykinin and ischemia: independent roles of PKC and prostaglandins

We have shown that the cyclooxygenase (COX) and protein kinase C (PKC) systems both contribute to afferent activation in response to bradykinin (BK) and abdominal ischemia. Because the contribution from PKC to C fiber activation may depend, in part, on prostaglandin production, we hypothesized that an intact COX system is required for PKC-induced activation of ischemically sensitive abdominal visceral afferents by BK and abdominal ischemia. Single-unit activity of abdominal visceral C fibers was recorded from the right thoracic sympathetic chain of anesthetized cats. Three repeated injections of BK (1-2 mu g/kg ia) produced similar increases in afferent activity from the baseline of 1.32 +/- 0.24, 1.37 +/- 0.32, and 1.41 +/- 0.24 impulses/s (n = 5). In another group of animals (n = 5), the second and third BK injections were performed after COX inhibition (indomethacin; 5 mg/kg iv) and then combined COX + PKC inhibition [PKC-(19-36), 20 mu g/kg iv], respectively. Inhibition of COX reduced (P < 0.05) the afferent response to BK (0.59 +/- 0.12 impulses/s) compared with the unblocked condition(1.14 +/- 0.27 impulses/ s), whereas combined COX + PKC inhibition further attenuated the increase from baseline (0.18 +/- 0.09 impulses/s; P < 0.05). Similar results were obtained in a third group of cats when the antagonists were administered in reverse order (n = 7). In a fourth group of cats (n = 9) that were pretreated with indomethacin, ischemia increased afferent activity (0.78 +/- 0.17 impulses/s). However, neural activity was attenuated (0.51 +/- 0.14 impulses/s; P < 0.05) during a second bout of ischemia in the presence of indomethacin + PKC-(19-36). These results suggest that the contribution from PKC to the activation of ischemically sensitive C fibers, particularly by BK, does not require an intact cyclooxygenase system.