title: Role of nitric oxide in the expression of hepatic vascular stress genes in response to sepsis.
abstract: This study examined the role of nitric oxide (NO) on the expression of the hepatic vasoregulatory gene during polymicrobial sepsis. Aminoguanidine (AG, 100 mg/kg) or Nomega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) was injected intraperitoneally at 0, 3, 6, 10, and 20 h after a cecal ligation and puncture (CLP). The heart rate increased 24 h after the CLP, and this increase was attenuated by L-NAME and further attenuated by AG. The mean arterial pressure in the CLP animals did not change significantly 24 h after the onset of sepsis but was increased after the L-NAME injection. Sepsis increased the serum aminotransferase levels, which were attenuated by AG but augmented by L-NAME. CLP increased the mRNA level of the ET-1 and ETB receptors in the liver. This increase was prevented by AG but augmented by L-NAME. The level of iNOS and HO-1 mRNA expression were increased by CLP, which was prevented by both AG and L-NAME. The level of TNF-alpha and COX-2 mRNA expression increased after CLP, and was attenuated by AG. These results show that iNOS and eNOS are regulated differently in sepsis. While eNOS appears to have a protective role in liver microcirculation, the strong upregulation of iNOS might contribute to a microvascular dysfunction and hepatic injury.
authors: College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, South Korea.
authors: Hyun-Ae
authors: HA
authors: Eum
authors: Sang-Won
authors: SW
authors: Park
authors: Sun-Mee
authors: SM
authors: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000235:genetics; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D000410:Alanine Transaminase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester