Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats

Yi Cheng Lu, Shanliang Liu, Qin Zhi Gong, Robert J. Hamm, Bruce G Lyeth

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

We examined the effects of N(ω)-nitro-L-arginine methyl ester (L- NAME), an inhibitor of nitric oxide synthase (NOS), on mortality, morbidity, and cardiovascular parameters following traumatic brain injury (TBI) in the rat. Rats were anesthetized with 2% isoflurane prior to moderate (2.0 atmosphere), central fluid percussion TBI. Temporalis muscle temperature was maintained at 37 ± 0.5°C. L-NAME (10 mg/kg iv) was administered once at either 5 min before, 5 min after, or 15 min after TBI. Sensorimotor deficits and spatial learning/memory deficits were assessed after injury. Separate groups of rats were monitored for cardiovascular parameters. Preinjury administration of L-NAME significantly increased mortality from 13 (vehicle) to 70% (associated with pulmonary edema), whereas postinjury, L-NAME had no effect on mortality (14 and 25%). L-NAME administered at 5 or 15 min after injury had no significant effect on motor performance or cognitive performance deficits associated with TBL L-NAME in uninjured rats increased arterial blood pressure by 25 mmHg within 2 min. L-NAME injected 5 min before TBI greatly prolonged the hypertensive episode associated with TBI (1 min in vehicle vs 60 min in L-NAME). L-NAME injected 5 min after TBI caused a sustained 35 mmHg increase in blood pressure. These findings suggest that acute inhibition of NOS has detrimental consequences on mortality that may be owing to its cardiovascular effects.

Original languageEnglish (US)
Pages (from-to)125-137
Number of pages13
JournalMolecular and Chemical Neuropathology
Volume30
Issue number1-2
StatePublished - Jan 1997
Externally publishedYes

Keywords

  • blood pressure
  • fluid percussion
  • L-NAME
  • morbidity
  • mortality
  • rat
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Molecular Biology
  • Neuroscience(all)

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