L-arginine does not improve cortical perfusion or histopathological outcome in spontaneously hypertensive rats subjected to distal middle cerebral artery photothrombotic occlusion

Ricardo Prado, Brant D. Watson, Weizhao Zhao, Hiroshi Yao, Raul Busto, W. Dalton Dietrich, Myron D. Ginsberg

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The potential of nitric oxide (NO) to influence positively or negatively the outcome of mechanically induced focal cerebral ischemia is still controversial. Recent evidence suggests that NO of vascular origin, whether synthesized from exogenously administered L-arginine (L-Arg) or from NO donor compounds, is beneficial but that of neuronal origin is not. However, the therapeutic potential of NO to ameliorate stroke induced by arterial thrombosis has not been reported. We assessed the therapeutic effect of L- Arg administration in spontaneously hypertensive rats (SHR) subjected to permanent photothrombotic occlusion of the distal middle cerebral artery (dMCA). The ipsilateral carotid artery was left unligated to enhance L-Arg delivery into the putative penumbral region. Local CBF (LCBF) was assessed at 30 min by the [14C]iodoantipyrine technique (n = 9), while histological infarct volumes and index of peripheral ischemic cell change were determined at 3 days (n = 7). Rats (n = 9) given 300 mg/kg L-Arg at 18 and 3 h before photothromboric dMCA occlusion and at 5 min afterward displayed no significant differences in LCBF compared with animals (n = 8) injected with water (the carrier vehicle) and similarly irradiated. Infarct volumes were also similar, being 37.0 ± 9.7 mm3 (SD) in the vehicle-treated and 49.1 ± 17.2 mm3 (SD) in the L-Arg-treated groups (both n = 7), as were assessments of ischemic neuronal density in the penumbra. In contrast, L-Arg administered intravenously in a dose of 300 mg/kg to nonischemic SHR (n = 5) increased cortical CBF by ~75% during a 70-min observation period. We conclude that thrombotic processes superimposed upon cerebral ischemia may facilitate tissue reactions that offset the potentially beneficial effect of L-Arg, and this caveat must be considered when proposing L-Arg for clinical treatment of focal thrombotic stroke.

Original languageEnglish (US)
Pages (from-to)612-622
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume16
Issue number4
DOIs
StatePublished - Jan 1 1996

Keywords

  • Cerebral blood flow
  • Cerebral ischemia
  • Endothelium-derived relaxing factor
  • Nitric oxide synthase activation
  • Photothrombosis

ASJC Scopus subject areas

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

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