title: Influence of selective nitric oxide synthetase inhibitor for treatment of refractory haemorrhagic shock.
abstract: OBJECTIVE
  Haemorrhagic shock (HS) is implicated in the induction of inducible nitric oxide synthase that leads to increased production of nitric oxide (NO). We investigated the influence of aminoguanidine (AG), a selective iNOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor and S-Nitroso-N-acetylpenicillamine (SNAP), a NO donor, each of which was given with (+) or without (-) angiotensin II (ANGII), a vasoconstrictor, on the survival rate of HS decompensatory phased (HSDP) rats.
  
  
  METHODS
  HSDP was achieved via a constant pressure method. Organs were harvested and analyzed from rats sacrificed 72 h after HSDP or upon death. Plasma collected from HSDP rats were used to measure nitrate/nitrite, GOT and creatinine levels.
  
  
  RESULTS
  AG+ANGII-treated rats had significantly higher survival rates compared to the other treatment groups, 72 h following HSDP. A marked increase in MABP level was observed in AG+ANGII-treated rats when compared to other treatment groups. Histological examinations also showed a reduction of organ damage in AG+ANGII-treated rats compared to other treatment groups. Nitrate/nitrite level, glutamic oxalacetic transaminase (GOT) level and creatinine level were also significantly improved in AG+ANGII-treated rats compared to the other groups.
  
  
  CONCLUSIONS
  A greater beneficial effect was achieved with treatment by the AG+ANGII combination. Our experiments showed that the inhibition of excessive NO formation that occurred during HSDP, had augmented the vascular responsiveness effect of ANGII following protracted HS.
authors.affiliation: Department of Pharmacology, National University of Singapore, Singapore, Singapore.
authors.forename: Md
authors.initials: M
authors.lastname: Shirhan
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Siew-Yang Low
authors.initials: SY
authors.lastname: Kerwin
authors.forename: Kian Chye
authors.initials: KC
authors.lastname: Ng
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001795:Blood Pressure Determination; D003404:Creatinine / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D006146:Guanidines; D000804:Angiotensin II; D009569:Nitric Oxide; D003404:Creatinine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester