Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats

1. Activation of abdominal sympathetic afferents during ischaemia reflexly excites the cardiovascular system. We have shown previously that exogenous 5-hydroxytryptamine (5-HT, i.e. serotonin) stimulates abdominal sympathetic afferent nerve endings, and recently have documented increased concentrations of 5-HT in intestinal lymph and portal venous plasma during brief abdominal ischaemia. The present investigation evaluated the role of endogenously produced 5-HT in activation of ischaemically sensitive abdominal sympathetic afferents. 2. Nerve activity of single-unit C fibre afferents innervating duodenum, mesentery, pancreas, por.tal hepatis, bile duct, gall bladder and jejunum was recorded from the right thoracic sympathetic chain of anaesthetized cats. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia. 3. Intra-arterial injection of 5-HT (20 mu g kg(-1)) increased discharge activity of twelve afferents from 0.23 +/- 0.05 to 0.96 +/- 0.09 impulses s(-1) after an onset latency of 5.7 +/- 1.4 s. Also, 2-methylserotonin (l00 mu g kg(-1) I.A.), a 5-MT3 receptor agonist, stimulated eleven of twelve afferents to significantly increase their discharge activity from 0.25+/-0.05 to 0.90 +/- 0.10 impulses s(-1) after a latency of 3.3 +/- 0.4 s. Furthermore, intravenous injection of tropisetron (200 mu g kg(-1)), a 5-MT3 receptor antagonist, significantly attenuated the increase in activity of twelve other C fibre afferents during 10 min of abdominal ischaemia from 1.62 +/- 0.18 to 0.94 +/- 0.22 impulses s(-1) and eliminated the response of eleven other afferents to 5-HT. 4. Both the 5-MT, receptor agonist, alpha-methylserotonin (100 mu g kg(-1), I.A.), and the 5-MT1 receptor agonist, 5-carboxamidotryptamine (100 mu g kg(-1), I.A.), did not alter the impulse activity of these twelve afferents (0.29 +/- 0.05 to 0.31 +/- 0.06, and 0.26 +/- 0.06 to 0 29 +/- 0 06 impulses s(-1), respectively). 5. Treatment with indomethacin (5 mg kg(-1) I.V.) in eight different cats did not alter the response of nine C fibre afferents to exogenous 5-HT (0.91 +/- 0.17 vs. 1.19 +/- 0.25 impulses s(-1) P > 0 05). 6. The results suggest that, during mesenteric ischaemia, endogenous 5-HT contributes to the activation of abdominal sympathetic afferents, mainly through direct stimulation of 5-MT, receptors and that the action of 5-HT on these afferents appears to be independent of the cyclo-oxygenase pathway.