Cholinergic Receptors in Human Brain Arteries and Microvessels

Abstract

Cholinergic mechanisms have long been known to be implicated in the regulation of cerebral blood flow (CBF). The parasympathetic control of brain superficial vessels and the intracerebral cholinergic regulation of cerebral cortex microvasculature are well described. In vivo administration of acetylcholine (ACh) or cholinomimetics, as well as stimulation of specific neuronal structures, result in CBF increasesensitive to muscarinic and/or nicotinic blockade. In vitro administration of ACh to human isolated brain arteries results almost exclusively in an endothelium-dependent relaxation.This prominent dilatory effect contrasts with the dual vasomotor response (dilatation followed by constriction at higher doses of ACh) observed in such species as the dog and cat. At the level of the intraparenchymal microvessels, ACh induces vasodilatationand could mediate functions such as the fine tuning of local CBFand possibly blood—brain barrier permeability. Recent evidence indicates that ACh is not a direct smooth muscle vasodilatory agent, but rather interacts with specific cholinergic receptors strategically located on nerve terminals and/or endothelial cells to modulate the synthesis and release of a relaxing factor.