Cholinergic inhibition of sympathetic vasoconstrictor tone in the cerebrovascular bed mediated by nicotinic-type receptors.
The cholinergic influence on the cerebrovascular bed was studied in cats and rabbits using a combination of in vitro and in vivo approaches. Isolated pial arteries were superfused with 3H-norepinephrine, and the efflux of tritium was studied under various conditions of transmural electrical stimulation of the perivascular sympathetic nerves. Field stimulation increased the radioactivity in the efflux in a frequency-dependent manner. The amount of tritium overflow (of which approximately 70% represents liberated radioactive norepinephrine) from the nerves during stimulation was enhanced by hexamethonium, the effect being inhibited by nicotine or acetylcholine. This action of nicotine and acetylcholine was counteracted by hexamethonium (but not by atropine). Carbachol infusion under in vivo conditions increased blood flow in the caudate nucleus as measured by thermoclearance. This effect was inhibited by atropine. Postganglionic stimulation of the cervical sympathetic chain above the superior cervical ganglion produced, in itself, a reduced local cerebral blood flow. The response (but not the flow reduction obtained by exogenous norepinephrine) was diminished during infusion with carbachol. The inhibition, amounting more than 50%, of the sympathetic nerve action on CN blood flow was not affected by atropine. It is concluded that (a) there are direct cholinergic dilator mechanisms in the cerebrovascular bed mediated by muscarinic-type of cholinergic receptors in the vascular smooth musculature, and (b) the perivascular adrenergic nerve terminals possess nicotinic-type of cholinergic receptors mediating an ihibition of the local norepinephrine release, probably through an action by the cholinergic nerve terminals, which run parallel to and in close association with the adrenergic axons separated only by a 25 nm distance.
D000818:Animals; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004558:Electric Stimulation; D005260:Female; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009638:Norepinephrine