Intervention with nitric oxide synthase inhibitors for traumatic shock in rats.
OBJECTIVE
To evaluate the effects of a selective inhibitor of inducible nitric oxide synthase (iNOS) aminoguanidine (AG) and a non-selective inhibitor of nitric oxide synthase (NOS) N(G)-nitro-L-arginine methylester (L-NAME) on traumatic shock in rats.


METHODS
Animal models of traumatic shock were established in 44 Sprague-Dawley rats following fractures in both femur shafts and subsequent depletion until the mean arterial pressure in the femoral artery dropped to 35 to 45 mmHg(4.67-6.00 kPa). Hypotension was maintained for 30 min before the collected blood was infused back into the rats supplemented with Ringer's solution of the same volume. The rat models were then randomly divided into 3 groups, namely traumatic shock group (n=10), AG group (which was subdivided into AGI, AGII, and AGIII groups, each consisting of 8 rats and receiving 2, 8, and 60 mg/kg x b.w AG infusion respectively during resuscitation), and L-NAME group (with 8 mg/kg x b.w L-NAME infusion during resuscitation, n=10). Plasma NO levels were determined before and after shock, immediately after resuscitation and 0.5, 2, 4 h after resuscitation, and the survival rates within 24 h were recorded with tissue samples of the lung, liver, kidney and intestine obtained 24 h after shock for microscopic examination.


RESULTS
Plasma NO level was seen to increase markedly after traumatic shock in the rat models. In the 3 AG groups, the elevated NO levels following the shock were obviously reduced after resuscitation with less tissue damages and higher survival rates, as compared with the other 2 groups. The best protective effect against traumatic shock was observed in AGIII group. In spite of obvious plasma NO level-lowering effect after resuscitation, L-NAME exhibited little efficacy in alleviating the tissue damages in the organs and hence failed to improve the survival rate of the rats.


CONCLUSIONS
NO plays an important role in the pathological process of traumatic shock, and the application of AG may improve the condition. L-NAME can decrease plasma NO level after resuscitation, but fail to improve the outcome of traumatic shock in rats.
Sun
Gao-bin
GB
Department of General Surgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. sungaobin5278@sina.com
Huang
Zong-hai
ZH
Sun
Ying-gang
YG
Yang
Wen-yu
WY
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000378:metabolism / Q000517:prevention & control*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester