Sympathetic modulation of nitrergic neurogenic vasodilation in cerebral arteries

The presence of close apposition between the adrenergic and the non-adrenergic or nitrergic nerve terminals in large cerebral arteries in several species is well documented. The axo-axonal distance between these different types of nerve terminals is substantially closer than the synaptic distance between the adventitial nerve terminals and the outermost layer of smooth muscle in the media. This feature suggests that a functional axo-axonal interaction between nerve terminals is more likely to occur than that between the nerve and muscle. Thus, transmitters released from one nerve terminal may modulate release of transmitters from the neighboring nerve terminals, resulting in a neurogenic response. We have reported that nicotine-induced nitric oxide (NO)-mediated neurogenic vasodilation is dependent on intact sympathetic innervation in porcine and cat cerebral arteries. Evidence also has been presented to indicate that nicotine acts on alpha(7)-nicotinic receptors located on sympathetic nerve terminals, resulting in release of norepinephrine which then diffuses to act on beta(2)-adrenoceptos located on the neighboring nitrergic nerve terminals to release NO and therefore vasodilation. The predominant facilitatory effect of beta(2)-adrenoceptors in releasing NO is compromised by presynaptic alpha(2)-adrenoceptors located on the same nerves. Activation of cerebral sympathetic nerves may cause NO-mediated dilation in large cerebral arteries at the base or the brain.