Neurochemicals involved in medullary control of common carotid blood flow

Abstract

The common carotid artery (CCA) supplies intra- and extra-cranial vascular beds. An area in the medulla controlling CCA blood flow is defined as the dorsal facial area (DFA) by Kuo et al. in 1987. In the DFA, presynaptic nitrergic and/or glutamatergic fibers innervate preganglionic nitrergic and/or cholinergic neurons which give rise to the preganglionic fibers of the parasympathetic 7th and 9th cranial nerves. Released glutamate from presynaptic nitrergic and/or glutamatergic fibers can activate N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors on preganglionic nitrergic and/or cholinergic neurons. By modulating this glutamate release, several neurochemicals including serotonin, arginine, nitric oxide, nicotine, choline and ATP in the DFA regulate CCA blood flow. Understanding the neurochemical regulatory mechanisms can provide important insights of the physiological roles of the DFA, and may help develop therapeutic strategies for diseases involving CCA blood flow, such as migraine, hypertensive disease, Alzheimer's disease and cerebral ischemic stroke.

Keywords: Carotid artery; Cerebral blood flow; Medulla; Neurotransmitter; Parasympathetic nucleus; Vascular regulation.

Fig. (1)

The DFA and its related connections. The DFA is located at the medulla dorsally to the facial nucleus. The preganglionic neurons in the DFA give rise to the preganglionic and postganglionic fibers of the parasympathetic 7^th and 9^th cranial nerves. The CCA vascular beds that supply intra- and extra-cranial tissues are innervated by the postganglionic fiber that releases acetylcholine. Muscarinic and nonmuscarinic action of acetylcholine is responsible for blood flow increase in the extra-cranial and intra-cranial tissues, respectively. Abbreviations: CCA, common carotid artery; DFA, dorsal facial area; FN, facial nucleus; 5SP, spinal trigeminal nucleus; 5ST, spinal trigeminal tract; PT, pyramidal tract.

Fig. (2)

Neurochemical modulations in the DFA. Preganglionic nitrergic and/or glutamatergic fiber and preganglionic nitrergic and/or cholinergic neurons contain the nNOS/GC/cGMP system. Nitric oxide (NO) and arginine may presynaptically activate the nNOS/GC/cGMP system in the preganglionic nitrergic and/or glutamatergic fiber to induce glutamate release, or postsynaptically activate that in the preganglionic nitrergic and/or cholinergic neurons to induce neuron firing (excitation). Other neurochemicals have their receptors on the preganglionic nitrergic and/or glutamatergic fiber but not on the preganglionic nitrergic and/or cholinergic neurons. Choline and nicotine may presynaptically activate nAChRs, while ATP and adenosine activate PR on the preganglionic nitrergic and/or glutamatergic fiber to enhance the nNOS/GC/cGMP activities in the fiber, resulting in glutamate release; nicotinic or choline action is mediated primarily via α7-nAChR, and purine/ATP action primarily via P2 receptor. However, 5-HT stimulation of 5HTR on the presynaptic nitrergic and/or glutamatergic fibers is mediated primarily by 5-HT2 receptor, probably through an inhibition of the nNOS/GC/cGMP activities leading to a reduction of glutamate release. The released glutamate in turn postsynaptically activates NMDA and AMPA receptors on the preganglionic nitrergic and/or cholinergic neurons. This activation may directly depolarize these neurons via NMDA or AMPA channels and/or indirectly depolarize preganglionic nitrergic and/or cholinergic neurons via activating their nNOS/GC/cGMP system. Consequently excitation impulses of the preganglionic nitrergic and/or cholinergic neurons are conducted through the pre- and post-ganglionic fibers of the parasympathetic 7^th and 9^th cranial nerves to CCA vascular beds for intra- and extra-cranial tissues, causing increase of blood flow in these tissues. Abbreviations: AMPAR, receptor for α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid; Arg, L-arginine; CAM, calmodulin; cGMP, cyclic guanosine monophosphate; 5HTR, serotonin receptor; GC, guanylyl cyclase; nAChR, nicotinic acetylcholine receptor; NMDAR, receptor for N-methyl- D-aspartate; NO, nitric oxide; nNOS, neuronal NO synthase; PR, purinergic receptor.