Neurotransmission in the sheep middle cerebral artery: modulation of responses by 5-HT and haemolysate

In ring sections of the sheep middle cerebral artery, electrical field stimulation elicits a complex response due to the simultaneous release of vasodilator and vasoconstrictor neurotransmitters. Haemolysate abolishes the relaxant effects of the vasodilator neurotransmitter and causes a marked augmentation of the contractile response in both the presence (448 +/- 191%) and absence (409 +/- 134%) of an intact endothelium. The haemolysate also reverses relaxation induced by sodium nitroprusside or sodium nitrite but has no effect on relaxation induced by 8-Br-cGMP. The vasodilator neurotransmitter therefore appears to act directly on the smooth muscle to cause relaxation by the stimulation of guanylate cyclase. The vasoconstrictor neurotransmitters that are released are antagonised by prazosin (100 nM), ketanserin (100 nM) and atropine (100 nM), which suggests that the transmitters involved are noradrenaline, 5-hydroxytryptamine (5-HT), and acetylcholine, respectively. In the presence of these three antagonists at 10 microM, there was 86.9 +/- 4.8% inhibition. Incubation with 5-HT (10 microM) causes a marked augmentation of the contractile response (267 +/- 56%) to field stimulation that can be reduced by pretreatment with either desipramine or citalopram, inhibitors of noradrenergic and serotoninergic uptake mechanisms, respectively. The 5-HT appears to be taken up into noradrenergic nerves and released as an alternative neurotransmitter upon subsequent stimulation. These actions of haemolysate and 5-HT may be involved in the cerebral vasospasm observed following subarachnoid haemorrhage.