Nitric oxide and the cerebral circulation.

Abstract

Nitric oxide (NO) is a potent vasodilator that was initially described as the mediator of endothelium-dependent relaxation (endothelium-derived relaxing factor, EDRF). It is now known that NO is produced by a variety of other cell types. Endothelium produces NO (EDRF) under basal conditions and in response to a variety of vasoactive stimuli in large cerebral arteries and the cerebral microcirculation. Endothelium-dependent relaxation is impaired in the presence of several pathophysiological conditions. This impairment may contribute to cerebral ischemia or stroke. Activation of glutamate receptors appears to be a major stimulus for production of NO by neurons. Neuronally derived NO may mediate local increases in cerebral blood flow during increases in cerebral metabolism. NO synthase-containing neurons also innervate large cerebral arteries and cerebral arterioles on the brain surface. Activation of parasympathetic fibers that innervate cerebral vessels produces NO-dependent increases in cerebral blood flow. Increases in cerebral blood flow during hypercapnia also appear to be dependent on production of NO. Astrocytes may release some NO constitutively, but astrocytes and microglia can release relatively large quantities of NO after induction of NO synthase in response to endotoxin or some cytokines. Expression of inducible NO synthase, perhaps in response to local production of cytokines, may exert cytotoxic effects in brain during or after ischemia. Because endothelium, neurons, and glia can all produce NO in response to some stimuli, the influence of NO on the cerebral circulation appears to be very important. Under normal conditions, constitutively produced NO influences basal cerebral vascular tone and mediates vascular responses to a diverse group of stimuli. The inducible form of NO synthase produces much greater amounts of NO that may be an important mediator of cytotoxicity in brain.

Differential Involvement of D1 and D2 Dopamine Receptors in L-DOPA-Induced Angiogenic Activity in a Rat Model of Parkinson's Disease

“…Accordingly, microvascular responses ought to be considered when evaluating the effects of either anti-or pro-dyskinetic treatments with unknown mechanisms of action. Intriguingly, some vasoactive substances, such as a 2 -adrenergic receptor antagonists (Zou and Cowley, 2000), nicotine (Hawkins et al, 2002), and nitric oxide synthase inhibitors (Faraci and Brian, 1994) exert strong anti-dyskinetic effects in animal models of PD (Fox et al, 2001;Padovan-Neto et al, 2009;Quik et al, 2007Quik et al, , 2008. Elucidating the effects of these treatments on microvascular physiology and angiogenesis in the brain will be an exciting task for future studies.…”

Innervation of Two Peptidergic (Substance P and Calcitonin gene-related peptide) Nerves in the Cerebral Arteries and Choroid Plexus of the Japanese Newt (Triturus pyrrhogaster).

“…The vasodilatory effect, of SP is dependent on the presence of vascular endothelium [9], caused by endothelium-derived releasing factors such as nitric oxide [14]. CGRP exerts a strong NANC vasodilation that is attributable to the direct action on vascular smooth muscles [20,27].…”

Polymorphisms of genes in nitric oxide-forming pathway associated with ischemic stroke in Chinese Han population

“…NO plays an important role in the control of cerebral blood flow, thrombogenesis, and the modulation of neuronal activity [4] . High concentrations of NO originating from cerebral ischemia mediate inflammatory and cytotoxic pathways leading to neuronal death [5] .…”

“…Several potential functional polymorphisms in the nitric oxide-forming pathway have recently been discovered, including (1) Leu608Ser (rs2297518) in inducible [iNOS] [7] , (2, 3) Glu298Asp (rs1799983) and T-786C (rs2070744) in the promoter region of endothelial [eNOS] [8][9][10][11][12] , (4,5) Tyr72His (rs4673) and C+640T (rs1049255) in the 3'-untranslated region (UTR) of the cytochrome b-245, alpha polypeptide gene (CYBA) [13][14][15][16] , which encodes the p22phox subunit of the NADPH oxidase, and (6) G+243A (rs841) in the 3'-UTR of the GTP cyclohydrolase 1 gene (GCH1) [17] . With special attention to the biological process of cerebral ischemia regulation, we investigated whether polymorphisms in these genes implicated in the pathway of NO formation are associated with IS in a large cohort in the Chinese Han population.…”