Inhibition of nitric oxide synthesis increases focal ischemic infarction in rat

Seiji Yamamoto, Eugene V. Golanov, Scott B. Berger, Donald J. Reis

Research output: Contribution to journalArticlepeer-review

208 Scopus citations


We investigated whether inhibition of nitric oxide (NO) biosynthesis with N-ω-nitro-L-arginine (NNA), a competitive inhibitor of NO synthase (NOS), would modify the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats. NNA was inside for 1 h (2.4 mg/kg/h) immediately following occlusion of the MCA. NNA increased lesion volume 24 h later by 32% over controls (150.8 ± 16.6 to 199.2 ± 17.4 mm3; p < 0.001, n = 6). This effect was antagonized by coinfusion of L- but not D-arginine. The antihypertensive rilmenidine (0.75 mg/kg) reduced the lesion by 27% (p < 0.05, n = 4). Changes in lesion size were confined to the penumbra. NNA increased arterial pressure (AP) (118 ± 8.9 to 149 ± 16.0 mm Hg; p < 0.01, n = 3) but did not change regional CBF. However, elevation of AP did not change the lesion volume or distribution. We conclude that inhibition of the constitutive form of NOS in vivo increases the volume of focal ischemic infarction as a consequence of reduced NO biosynthesis. The absence of NO availability may extend lesion formation by inhibition of reactive hyperemia, platelet disaggregation, and/or release of neuroprotective neuromodulators in the penumbra, which may counteract and override any of its neurotoxic actions.

Original languageEnglish (US)
Pages (from-to)717-726
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number5
StatePublished - 1992


  • Focal cerebral ischemia
  • N-ω-Nitro-L-arginine
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism


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