The complex role of nitric oxide in the pathophysiology of focal cerebral ischemia.
Nitrogen monoxide (NO) has recently emerged as an important mediator of cellular and molecular events which impacts the pathophysiology of cerebral ischemia. Although tempting to ask whether NO is "good or bad" for cerebral ischemia, the question underestimates the complexities of NO chemistry and physiology as well as oversimplifies the pathophysiology of focal cerebral ischemia. Important vascular and neuronal actions of NO have been defined which both enhance tissue survival and mediate cellular injury and death, and these will be reviewed. Strategies which modify NO synthesis and/or metabolism may someday assume therapeutic importance, but not until the tissue compartments generating NO, the activities of the enzymes that are inducibly and constitutively expressed, and the redox state of NO during the stages of ischemic injury, are defined with greater precision. Our knowledge of these processes is rudimentary. This review will summarize the evidence from animal models which supports an emerging role for NO in ischemic pathophysiology. Important aspects of NO synthesis and inhibitors of this process will also be discussed.
Dalkara
T
T
Department of Neurosurgery and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Moskowitz
M A
MA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism*; D002415:Cats; D016923:Cell Death; D002544:Cerebral Infarction / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010101:Oxygen Consumption; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases