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 language | English (US) |
|---|---|
| Pages (from-to) | 125-137 |
| Number of pages | 13 |
| Journal | Molecular and Chemical Neuropathology |
| Volume | 30 |
| Issue number | 1-2 |
| State | Published - Jan 1997 |
| Externally published | Yes |
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Keywords
- blood pressure
- fluid percussion
- L-NAME
- morbidity
- mortality
- rat
- traumatic brain injury
ASJC Scopus subject areas
- Clinical Neurology
- Molecular Biology
- Neuroscience(all)
Cite this
Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats. / Lu, Yi Cheng; Liu, Shanliang; Gong, Qin Zhi; Hamm, Robert J.; Lyeth, Bruce G.
In: Molecular and Chemical Neuropathology, Vol. 30, No. 1-2, 01.1997, p. 125-137.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats
AU - Lu, Yi Cheng
AU - Liu, Shanliang
AU - Gong, Qin Zhi
AU - Hamm, Robert J.
AU - Lyeth, Bruce G
PY - 1997/1
Y1 - 1997/1
N2 - 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.
AB - 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.
KW - blood pressure
KW - fluid percussion
KW - L-NAME
KW - morbidity
KW - mortality
KW - rat
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=0031052459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031052459&partnerID=8YFLogxK
M3 - Article
C2 - 9138424
AN - SCOPUS:0031052459
VL - 30
SP - 125
EP - 137
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1-2
ER -