The effects of N(G)-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits.
Little is known about the role of nitric oxide in the pathophysiology of spinal cord ischemia. We evaluated the effects of nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine-methyl ester (L-NAME) in rabbits whose abdominal aorta was occluded for 20 min (Experiment 1) or 25 min (Experiment 2). In Experiment 1, the L-NAME group (n = 6) received 3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion. Ischemia was induced 20 min after the start of L-NAME. The phenylephrine group (n = 6) received phenylephrine to maintain comparable blood pressure. The control group (n = 6) received saline. In Experiment 2, L-NAME (3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion) and phenylephrine groups (n = 6 each) were studied. Ischemia was induced 100 min after the start of L-NAME. Forty-eight hours after reperfusion, hindlimb motor function and histopathology of the spinal cord were examined. In Experiment 1, L-NAME and phenylephrine both improved neurologic outcome, with higher intraischemic blood pressures than saline. In Experiment 2, L-NAME worsened the neurologic and histopathologic outcome compared with phenylephrine. Attenuation of damage by L-NAME in Experiment 1 may be attributable to an intraischemic blood pressure increase. The worse outcome with L-NAME in Experiment 2 suggests that NOS inhibition exacerbates ischemic spinal cord damage.


CONCLUSIONS
Nonselective inhibition of nitric oxide synthase activity has aggravating effects on the neurologic and histopathologic outcome after transient spinal cord ischemia.
Matsumoto
M
M
Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Ube, Japan.
Iida
Y
Y
Wakamatsu
H
H
Ohtake
K
K
Nakakimura
K
K
Xiong
L
L
Sakabe
T
T
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015424:Reperfusion; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester