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      Induction of Nitric Oxide and Tetrahydrobiopterin Synthesis by Lipoteichoic Acid from Staphylococcus aureus in VascularSmooth Muscle Cells


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          Lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria, induces an isoform of nitric oxide (NO) synthase (iNOS) in vascular smooth muscle; this process may be associated with the vascular failure observed in gram-positive septic shock. The aim of the present work was to study the cellular mechanisms involved in the induction of NO synthesis by LTA from Staphylococcus aureus in cultured rat vascular smooth muscle cells. LTA induces the gene expression of iNOS and GTP cyclohydrolase I (GTPCH) as well as the formation of NO and tetrahydrobiopterin (BH4), effects which are synergistic with interferon-γ. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTPCH, inhibits both the increase in cellular levels of BH4 as well as the concomitant formation of NO caused by LTA in combination with interferon-γ. This inhibition by DAHP is reversed by co-addition of sepiapterin which is a substrate for BH4 synthesis. Thus, BH4 synthesis is an absolute requirement for the induction of NO synthesis by LTA in vascular smooth muscle. Our findings also suggest that interrupting pterin synthesis may be an effective target for pharmacologic interventions aimed at limiting NO overproduction in gram-positive shock.

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          Cloning of Inducible Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells

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            GTP Cyclohydrolase I mRNA Is Induced by LPS in Vascular Smooth Muscle: Characterization, Sequence and Relationship to Nitric Oxide Synthase

             Y Hattori,  S.S. Gross (1993)

              Author and article information

              J Vasc Res
              Journal of Vascular Research
              S. Karger AG
              April 1998
              16 April 1998
              : 35
              : 2
              : 104-108
              a Department of Endocrinology, Dokkyo University School of Medicine, Mibu, b Department of Biochemistry, Meikai University School of Dentistry, Sakado, Japan; c Department of Pharmacology, Cornell University Medical College, New York, N.Y., USA; d The William Harvey Research Institute, St. Bartholomew’s Hospital Medical College, London, UK
              25571 J Vasc Res 1998;35:104–108
              © 1998 S. Karger AG, Basel

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              Page count
              Figures: 3, References: 22, Pages: 5
              Research Paper


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