Elsevier

Neuropharmacology

Volume 33, Issue 11, November 1994, Pages 1447-1452
Neuropharmacology

Dual role of nitric oxide in focal cerebral ischemia

https://doi.org/10.1016/0028-3908(94)90048-5Get rights and content

Abstract

The importance of nitric oxide (NO) in the pathophysiology of cerebral ischemia was examined following middle cerebral artery occlusion in rats. A significant increase in infarct size developed following inhibition of NO synthase (NOS) activity by l-arginine analogues whereas intravenous l-arginine dosedependently decreased infarct volume in the same models. Protection after l-arginine administration was associated with enhanced blood flow within the perinfarct zone as demonstrated by simultaneous recording of rCBF and electrocorticogram activity within subjacent brain. Selective NOS inhibition by 7-nitroindazole (7-NI) significantly reduced infarct volume at doses of 25 and 50 mg/kg and in amounts that did not decrease the response of pial vessels to topical acetylcholine. Together these data suggest that enhanced NO production within the cerebrovasculature protects brain tissue during focal ischemia via hemodynamic mechanisms whereas neuronal overproduction may facilitate or mediate neurotoxicity. Recent data using transgenic animals lacking NOS activity support the latter conclusion.

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