Effects of aminoguanidine and L-arginine methyl ester resuscitation following induction of fluid-percussion injury and severe controlled hemorrhagic shock in the rat brain.
OBJECTIVE
In this study the authors compared the effects of both a selective inducible nitric oxide synthase (iNOS) inhibitor and a nonselective inhibitor on posttraumatic recovery and neuron survival by using a combined model of lateral fluid-percussion injury (FPI) and hemorrhagic shock (HS).


METHODS
Male Sprague-Dawley rats weighing 300 to 350 g underwent FPI to the brain (3.5 atm) and hemorrhage to a mean arterial blood pressure (MABP) of 40 mm Hg for 1 hour. Rats were then resuscitated during 1 hour with bolus infusions of aminoguanidine (AG) or nitro-L-arginine methyl ester (L-NAME). Neuronal apoptosis was determined by performing Nissl staining and in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique. Rats infused with AG showed a significant increase in mean survival time and cerebral tissue perfusion, although the MABP and nitrate/nitrite levels did not significantly change compared with those in L-NAME-treated rats even though both animal groups had been subjected to combined FPI and HS, FPI alone, or HS alone. Furthermore, infusion of AG also significantly decreased the number of apoptotic neurons when compared with the number in rats treated with L-NAME.


CONCLUSIONS
The authors asserted that treatment with AG, which causes the inhibition of iNOS, might contribute to improved physiological parameters and neuronal cell survival following FPI and HS.
Atan
Md Shirhan
MS
Department of Pharmacology, National University of Singapore, Singapore.
Moochhala
Shabbir M
SM
Ng
Kian Chye
KC
Low
Kerwin
K
Teo
Ai Ling
AL
Lu
Jia
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate
D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester