Role of 5‐HT 3 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, portal 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 μg 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 (100 μg kg −1 , i.a.), a 5‐HT 3 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 μg kg −1 ), a 5‐HT 3 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‐HT 2 receptor agonist, α‐methylserotonin (100 μg kg −1 , i.a.), and the 5‐HT 1 receptor agonist, 5‐carboxamidotryptamine (100 μg 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‐HT 3 receptors and that the action of 5‐HT on these afferents appears to be independent of the cyclo‐oxygenase pathway.