Inhibition of vasodilator neurotransmission in the sheep middle cerebral artery by VIP antiserum

1. Middle cerebral artery rings from the sheep were relaxed by vasoactive intestinal peptide (VIP) (20-200 nM) or by stimulation of the vasodilator nerves, electrical field stimulation (EFS). 2. VIP antiserum 1:256 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-immune serum was inactive. 3. Capsaicin (1 microM) produced a transient relaxation but did not alter the response to EFS which was subsequently inhibited by addition of L-NOArg (100 microM). VIP-induced relaxation was antagonized by L-NOArg (50 microM) (from 68 +/- 5 to 46 +/- 2% relaxation 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 prevented by preincubation with L-NOArg (100 microM) but not D-NOArg. 5. VIP and neuronal NOS immunoreactivity was co-localized to the same adventitial nerve fibres in the sheep middle cerebral artery. 6. These results provide evidence that neurogenic relaxation in the sheep middle cerebral artery is, at least in part, mediated by VIP, involving activation of NO synthase.