Preservation of neurological functions by nitric oxide synthase inhibitors following hemorrhagic shock.
Excessive production of nitric oxide (NO) as result of inducible nitric oxide synthase (iNOS) induction has been implicated in the pathophysiology of hemorrhagic shock. Our aim was to study the effect of iNOS inhibitors, L-canavanine (50mg/kg) and N(G)-nitro- L-arginine methyl (L-NAME, 10mg/kg) and a resuscitation fluid, lactated Ringer's solution (3 times amount of blood lost), on survivability and neurological functions in rodents subjected to hemorrhagic shock. L-canavanine-treated rats had significantly higher survival rates (75%) compared to L-NAME-treated rats (44%) and lactated Ringer's solution-treated rats (40%), 72 h following hemorrhagic shock. A marked increase in the neurological performance was observed in L-canavanine-treated rats over the three-day period. Histological examinations also showed a reduction of degenerating neurons in L-canavanine-treated rats when compared to L-NAME-, lactated Ringer's solution- or un-treated rats. Mean arterial blood pressure (MABP), nitrate/nitrite level, glutamic oxalacetic transaminase (GOT) level, and blood gases were also significantly improved in L-canavanine-treated rats when compared to those of L-NAME-, lactated Ringer's solution- or un-treated rats. In conclusion, L-canavanine-treated rats were able to improve survivability, attenuate organ damage, and improve neurological outcome when compared to other treatment groups. It is therefore suggest that L-canavanine may be beneficial as a potentially useful therapeutic agent in treating neurological deficit as a result of hemorrhagic shock.
Ng
Kian Chye
KC
Defense Medical Research Institute, Defense Science & Technology Agency, 18 Medical Drive, #01-06, MD2, NUS, Singapore 117579, Singapore.
Moochhala
Shabbir M
SM
Md
Shirhan
S
Yap
Ee Lin
EL
Low
Siew Yang
SY
Lu
Jia
J
D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002172:Canavanine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018737:Hand Strength / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D019344:Lactic Acid / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D015996:Survival Rate; D013997:Time Factors
D004791:Enzyme Inhibitors; D019344:Lactic Acid; D002172:Canavanine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D019331:NG-Nitroarginine Methyl Ester