Localization of inducible nitric oxide synthase in vascular tissue in endotoxic shock

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Wakayama Medical College
• Principal Investigator: YAMAMOTO Manabu Wakayama Medical College Department of Anesthesia Assistant Professor, 医学部, 助手 (90281279)
• Co-Investigator(Kenkyū-buntansha): HATANO Yoshio Wakayama Medical College Department of Anesthesia Professor, 医学部, 教授 (70115913)
• Project Period (FY): 1996 – 1997
• Keywords: Nitric oxide synthase / vascular tissue / in situ hybridization / immunohistochemistry

Research Abstract

(1)Endotoxic shock was induced by injecting lipopolysaccharide (LPS) intraperitoneally to Wister rats. Aortae from rats treated with LPS for 4 hours showed hyporesponsiveness to phenylephrine. This hyporeactivity was reversed by administration of N^<omega>-Nitro-L-arginine, an inhibitor of nitric oxide synthase.
(2)The study using in situ hybridization showed that treatment with LPS for 4h induced expression of inducible nitric oxide synthase (iNOS)mRNA in the aortic wall. The signals for iNOS mRNA were localized in the non-vascular smooth muscle cells (VSMCs) in the tunica adventitia, and not in VSMCs in the tunica media.
(3)Immunohisotchemistry study using anti rat iNOS sntibody showed that iNOS-like immunorectivity was identified in the tunica adventitia of aortae from rats treated with LPS.
The findings of the present study confirm that LPS administration induces vascular hyporeactivity which is attributable to iNOS induction. The results in in situ hybridization study and immunohisotochemistry study suggest that iNOS induced in the perivascular non-VSMCs is involved in the pathogenesis of endotoxic shock.
The study on the heterogeneity in nitric oxide synthase induction in vascular tissues from different organs is now under way in our laboratory.

Research Products

• [Publications] Iranami H, Hatano Y, et al.: "A beta-adrenoreceptor agonist evokes a nitric oxide-cGMP relaxation mechanism modulated by adenylate cyclase in rat aorta" Anesthesiology. 85. 1129-1138 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ooka T, Hatano Y, et al.: "Protective effects of human urinary thipsin inhibitor in rat aorta" Crit Care Med. 24. 1903-1907 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogawa K, Yamamoto M et al.: "Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral artery" Can J Anaesth. 44. 426-432 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamamoto M, Hatano Y.et al.: "Different effects of hulothane,isoflurane and sevoflurane on sarcoplusmin reticalum of vascular smooth muscle in dog mesenteric artery" Acta Anaesth Scand. 41. 376-380 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iranami H, Hatano Y, et al.: "Halothane inhibition of acetylcholine-induced relaxation in rat mesenteric artery and aorta" Can J Anaesth. 44. 1196-1203 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamamoto, Hatano Y.et al.: "Holothane and isoflurane affenuate the relaxant response to nonadrenergic noncholinergic nerve stimulation of isolated canine cerebral artery" Anesth Analy. 86. 552-556 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iranami H,Hatano Y,Tsukiyama Y,Maeda H,Mizumoto K: "A beta-adrenoreceptor agonist evokes a nitric oxide-cGMP relaxation mechanism modulated by adenylate cyclase in rat aorta." Anesthesiology. 85. 1129-1138 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ooka T,Hatano Y,Yamamoto M,Ogawa K,Saika S.: "Prorective effects of human urinary trypsin inhibitor in rat aorta." Crit Care Med. 24. 1903-1907 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hirakata H,Ushikubi F,Toda H,Nakamura K,Sai S,Urabe N,Hatano Y,Narumiya S,Mori K: "Sevoflurane inhibits human platelet aggregation and thromboxane A2 formation, possibly by supression of cyclooxygenase activity." Anesthesiology. 85. 1447-1453 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ogawa K,Yamamoto M,Mizumoto K,Hatano Y.: "Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries." Can J Anaesth. 44. 426-432 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamamoto M,Hatano Y,Kakuyama M,Nakamura K,Tachibana T,Maeda H,Mori K: "Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery." Acta Anaesth Scand. 41. 376-380 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iranami H,Hatano Y,Tsukiyama Y,Yamamoto M,Maeda H,Mizumoto K: "Inhibitory action by halothane on acethylcholine-induced relaxation is less potent in mesenteric artery." Can J Physiol. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iranami H,Hatano Y,Tsukiyama Y,Yamamoto M,Maeda H,Mizumoto K: "Halothane inhibition of acetylcholine-induced relaxation in rat mesentereic arteri and aorta." Can J Anaesth. 44. 1196-1203 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamamoto M,Hatano Y,Oagawa K,Iranami H,Tajima T: "Halothane and isoflurane attenuate the relaxant response to nonadrenergic noncholineregic nerve stimulation of isoleted canine cerebral arteries." Anesth Analg. 86. 552-556 (1998)
  • Description: 「研究成果報告書概要(欧文)」より