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

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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.

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Lu, Y. C., Liu, S., Gong, Q. Z., Hamm, R. J., & Lyeth, B. G. (1997). Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats. Molecular and Chemical Neuropathology, 30(1–2), 125–137. https://doi.org/10.1007/BF02815154

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