INHIBITION OF VASODILATOR NEUROTRANSMISSION IN THE SHEEP MIDDLE CEREBRAL-ARTERY BY VIP ANTISERUM

1 Middle cerebral artery rings from the sheep were relaxed by vasoacti ve intestinal peptide (VIP) (20-200 nM) or by stimulation of the vasod ilator nerves, electrical field stimulation (EFS). 2 VIP antiserum 1:2 56 inhibited the relaxation produced by both exogenous VIP (from 70 +/ - 5 to 32 +/- 9% of 5-HT-induced tone at 200 nM VIP) and by EFS (from 43 +/- 5 to 26 +/- 6% of 5-HT-induced tone after 20 min), while pre-im mune serum was inactive. 3 Capsaicin (1 mu M) produced a transient rel axation but did not after the response to EFS which was subsequently i nhibited by addition of L-NOArg (100 mu M). VIP-induced relaxation was antagonized by L-NOArg (50 mu M) (from 68 +/- 5 to 46 +/- 2% relaxati on of 5-HT-induced tone) but not by D-NOArg. 4 Exogenous VIP produced an approximately 2.4-fold increase in cyclic GMP content which was pre vented by preincubation with L-NOArg (100 mu M) but not D-NOArg. 5 VIP and neuronal NOS immunoreactivity was co-localized to the same advent itial nerve fibres in the sheep middle cerebral artery. 6 These result s provide evidence that neurogenic relaxation in the sheep middle cere bral artery is, at least in part, mediated by VIP, involving activatio n of NO synthase.