0000000000885118

AUTHOR

Jürgen Schrader

Effects of nitric oxide donors on cardiac contractility in wild-type and myoglobin-deficient mice

1. The effects of the nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP), sodium(Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate), and (Z)-1-[N-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate) on force of contraction (F(c)) were studied in atrial and ventricular muscle strips obtained from wild-type (WT) and myoglobin-deficient (myo(-/-)) mice. 2. SNAP slightly reduced F(c) in preparations from WT mice at concentrations above 100 microM; this effect was more pronounced in myo(-/-) mice. 3. DEA-NONOate reduced F(c) in preparations from myo(-/-) mice to a larger extent than those from WT mice. 4. DETA-NONOate reduced F(c) in preparations…

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Production of Extracellular Adenosine by CD73+ Dendritic Cells Is Crucial for Induction of Tolerance in Contact Hypersensitivity Reactions

Dendritic cells (DCs) express the ecto-5′-nucleotidase CD73 that generates immunosuppressive adenosine (Ado) by dephosphorylation of extracellular Ado monophosphate and diphosphate. To investigate whether CD73-derived Ado has immune-suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to skin of wild-type (WT) or CD73-deficient (CD73–/–) mice, followed by sensitization and challenge with 2,4-dinitrofluorobenzene. In this model, we show the induction of tolerance by DNTB against 2,4-dinitrofluorobenzene only in WT but not in CD73–/– mice. Analysis of skin DCs showed increased expression of CD73 after application of DNTB in WT mice. That was accompanied by elevated concentrati…

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Dexamethasone lacks effect on blood pressure in mice with a disrupted endothelial NO synthase gene.

Cushing's syndrome and systemic administration of glucocorticoids are associated with hypertension, but the underlying molecular mechanism is only partially understood. We have shown previously that dexamethasone downregulates the expression of the endothelial NO synthase (eNOS) gene in human endothelial cells and in the rat and that this may contribute to the blood pressure-raising effect of the steroid [Proc. Natl. Acad. Sci. USA 96 (1999) 13357]. In the current communication, we demonstrated that dexamethasone increased mean arterial blood pressure in wild-type C-57 Bl6 mice (eNOS+/+ mice), but had no effect on blood pressure in mice with a disrupted eNOS gene (eNOS-/- mice) derived from…

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