Hattori Y, Hattori S, Motohashi S, Kasai K, Shimoda S I, Nakanishi N
Department of Endocrinology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Mol Cell Biochem. 1997 Jan;166(1-2):177-81. doi: 10.1023/a:1006875707028.
Induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) in the myocardium is implicated as a mechanism in the development of cardiac depression in immune activated states associated with an enhanced release of cytokines, such as septic shock. We evaluated the in vivo synthesis of NO and tetrahydrobiopterin (BH4), a cofactor of NOS, in the heart tissue using a model of LPS injection in rats (LPS: 10 mg/kg, i.v.). In control rats, iNOS activity or iNOS mRNA in the heart was negligible. Three hours after LPS administration, a marked induction of iNOS mRNA and activity was observed in the heart. A significant increase in BH4 content and GTP cyclohydrolase mRNA abundance was also observed in the heart from LPS-treated rats. Our results demonstrate induction of NO synthesis and parallel increase in BH4 concentration in the heart of rats after LPS treatment in vivo and may provide molecular evidence responsible for the increased production of BH4 which may up-regulate iNOS activity in the heart in vivo.
心肌中诱导型一氧化氮（NO）合酶（iNOS）的诱导被认为是与细胞因子释放增加相关的免疫激活状态下心脏抑制发展的一种机制，如脓毒性休克。我们使用大鼠静脉注射脂多糖（LPS：10mg/kg）模型评估了心脏组织中NO和NOS辅因子四氢生物蝶呤（BH4）的体内合成。在对照大鼠中，心脏中的iNOS活性或iNOS mRNA可以忽略不计。给予LPS三小时后，在心脏中观察到iNOS mRNA和活性的显著诱导。在LPS处理大鼠的心脏中也观察到BH4含量和GTP环化水解酶mRNA丰度的显著增加。我们的结果表明，体内LPS处理后大鼠心脏中NO合成的诱导以及BH4浓度的平行增加，并且可能提供负责BH4产生增加的分子证据，这可能在体内上调心脏中的iNOS活性。
