Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats.
We examined the effects of N omega-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 degrees 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 TBI. 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.
Lu
Y C
YC
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298, USA.
Liu
S
S
Gong
Q Z
QZ
Hamm
R J
RJ
Lyeth
B G
BG
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000097:blood; D016009:Chi-Square Distribution; D003071:Cognition / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009017:Morbidity; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000097:blood; D011654:Pulmonary Edema; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002245:Carbon Dioxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester