Role of nitric oxide in the expression of hepatic vascular stress genes in response to sepsis.
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.
Eum
Hyun-Ae
HA
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, South Korea.
Park
Sang-Won
SW
Lee
Sun-Mee
SM
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
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