Role of nitric oxide in hemorrhagic shock-induced bacterial translocation.
BACKGROUND
Hemorrhagic shock-induced bacterial translocation is an etiologic factor in the pathogenesis of multiple system organ damage. Excessive production of nitric oxide (NO) during hemorrhagic shock may lead to cellular injury and gut barrier failure that promotes bacterial translocation. We investigated the effect of aminoguanidine (AG) and N(G)-nitro-l-arginine methyl ester (l-NAME), both inhibitors of NO synthase, on hemorrhagic shock- induced bacterial translocation in the rat.


METHODS
Anesthetized male Sprague-Dawley rats were subjected to a hemorrhagic shock protocol for 30 min followed by intravenous injection (1 mL/kg body wt) with normal saline, AG (100 mg/kg), or l-NAME (10 mg/kg). Tissues/organs were examined histologically for damage and bacterial translocation. Plasma nitrate/nitrite was measured using a procedure based on the Griess reaction, and nitric oxide synthase (NOS) expression was determined immunohistochemically.


RESULTS
The shocked animals treated with saline died within 90 min, and deaths were associated with 100% bacterial translocation, increased tissue/organ damage, and elevated nitrate/nitrite production. In contrast, both AG and l-NAME increased the survival time of shocked rats to >72 h, abrogated bacterial translocation, reduced tissue/organ damage, and prevented excessive nitrate/nitrite production and upregulation of expression of endothelial NOS and inducible NOS.


CONCLUSIONS
Prevention of bacterial translocation by pharmacologic agents such as aminoguanidine and l-NAME could be an important therapeutic approach to lessen mortality rates following hemorrhagic shock.
Hua
T C
TC
Defence Medical Research Institute, Ministry of Defence, Singapore, 109681.
Moochhala
S M
SM
D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D016019:Survival Analysis; D013997:Time Factors
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester