title: Nitric oxide and nitrosothiols in cerebrovascular and neuronal regulation.
abstract: BACKGROUND
  Currently prevailing concepts concerning the endothelium-dependent relaxant effect of acetylcholine and other endothelium-dependent agonists are that it is mediated by the generation from arginine of nitric oxide, which is then released into the extracellular space, diffuses to the vascular smooth muscle, and activates soluble guanylate cyclase by combining with the iron of the heme component of the enzyme.
  
  
  CONCLUSIONS
  Recent studies show that in the cerebral circulation these traditional concepts need to be modified in two major areas. First, the activation of soluble guanylate cyclase by nitric oxide, nitroglycerin, or nitroprusside is indirectly mediated via release of calcitonin gene-related peptide from sensory nerve fibers. This peptide then activates soluble guanylate cyclase by an unknown mechanism. Second, the endothelium-derived relaxing factor from cerebral arterioles is not nitric oxide but a nitric oxide-containing compound, very likely a nitrosothiol. Nitrosothiols activate soluble guanylate cyclase in cerebral arterioles by direct action independent of calcitonin gene-related peptide. The participation of nitric oxide, nitrosothiols, or both in the regulation of basal cerebral vascular tone, in flow-dependent dilation, in the vascular responses to CO2, and in response to activation of the N-methyl-D-aspartic acid receptor are considered.
authors.affiliation: Department of Pathology, Medical College of Virginia, Richmond 23298.
authors.forename: H A
authors.initials: HA
authors.lastname: Kontos
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
chemical_list: D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide