Endothelium-derived relaxing factor in brain blood vessels is not nitric oxide.
BACKGROUND
The endothelium-derived relaxing factor that mediates the actions of acetylcholine is now most frequently identified as nitric oxide. Nitric oxide is believed to have numerous important regulating actions in neurons, blood vessels, and several other biological systems.


RESULTS
The literature concerning tissue other than cerebral blood vessels supports the conclusion that the endothelium-derived relaxing factor for acetylcholine is either nitric oxide or a compound formed from and containing nitric oxide (for example, a nitrosothiol). However, papers can be found indicating that this endothelium-derived mediator is not nitric oxide. In brain blood vessels the evidence is strongly against the conclusion that nitric oxide is the endothelium-derived mediator for acetylcholine. If this mediator is formed from nitric oxide, either in brain vessels or in other vessels, no data are available delineating how this synthesis is regulated or whether and where nitric oxide leaves the nitroso compound to initiate dilation. Indeed, cerebrovascular data now cast doubt on the commonly held belief that nitrosovasodilators regulate vascular tone by giving off nitric oxide to vascular smooth muscle.


CONCLUSIONS
In brain blood vessels the chemical identity of the endothelium-derived relaxing factor mediating the action of acetylcholine is unknown, but this relaxing factor does not appear to be nitric oxide. If the mediator contains nitric oxide, as is probably the case, the means by which it activates vascular guanylate cyclase and/or produces dilation is unknown. Since this relaxing factor inhibits platelet adhesion/aggregation in cerebral vessels as well as relaxing these vessels, the chemical identification of this relaxing factor and the elucidation of its mode of action are extremely important to our understanding and control of cerebrovascular phenomena in health and disease.
Department of Pathology (Neuropathology), Virginia Commonwealth University-Medical College of Virginia, Richmond.
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Rosenblum
D000109:Acetylcholine; D000818:Animals; D001921:Brain / Q000098:blood supply; D001923:Brain Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000187:drug effects; D009569:Nitric Oxide / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D014664:Vasodilation
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000109:Acetylcholine