| Abstract: | 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 μm ) produced a transient relaxation but did not alter the response to EFS which was subsequently inhibited by addition of L -NOArg (100 μM ). VIP-induced relaxation was antagonized by L -NOArg (50 μM ) (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 μM ) 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. |
