The effects of N(G)-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits.

Abstract

UNLABELLED:

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.

IMPLICATIONS:

Nonselective inhibition of nitric oxide synthase activity has aggravating effects on the neurologic and histopathologic outcome after transient spinal cord ischemia.

• Authors: M Matsumoto, Y Iida, H Wakamatsu, K Ohtake, K Nakakimura, L Xiong, T Sakabe
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 89 Issue 3 Pg. 696-702 (Sep 1999) ISSN: 0003-2999 [Print] United States
• PMID: 10475308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Vasoconstrictor Agents
• Phenylephrine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Blood Gas Analysis
• Blood Pressure (drug effects)
• Body Temperature
• Enzyme Inhibitors (pharmacology)
• Evoked Potentials
• Heart Rate (drug effects)
• Ischemia (pathology, physiopathology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type I
• Oxygen Consumption (drug effects)
• Phenylephrine (pharmacology)
• Rabbits
• Regional Blood Flow (drug effects, physiology)
• Reperfusion
• Spinal Cord (blood supply, pathology)
• Vasoconstrictor Agents (pharmacology)