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1.
Acta Physiol (Oxf) ; 213(3): 722-30, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25219340

ABSTRACT

AIM: This study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high-salt diet and/or hypoxia. METHODS: C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to 3-h exposure to hypoxia (8% O2) and/or 2 weeks of high-salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS). RESULTS: In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high-salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high-salt diet had approx. 150% higher glomerular ET-1 mRNA expression compared with a normal-salt diet (P < 0.05). High-salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor-selective antagonist, ABT-627, significantly attenuated the increase in glomerular ROS production produced by high-salt diet. In addition, chronic infusion of C57BL6/J mice with a subpressor dose of ET-1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment. CONCLUSION: These data suggest that both hypoxia and a high-salt diet increase glomerular ROS production via endothelial-derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1-induced nephropathy.


Subject(s)
Endothelin-1/administration & dosage , Hypoxia/metabolism , Kidney Diseases/metabolism , Kidney Glomerulus/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Sodium Chloride, Dietary/adverse effects , Animals , Disease Models, Animal , Endothelin A Receptor Antagonists/pharmacology , Endothelin-1/deficiency , Endothelin-1/genetics , Hypoxia/complications , Kidney Diseases/etiology , Kidney Diseases/genetics , Kidney Diseases/physiopathology , Kidney Glomerulus/drug effects , Kidney Glomerulus/physiopathology , Male , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress/drug effects , Proteinuria/metabolism , Proteinuria/physiopathology , Receptor, Endothelin A/drug effects , Receptor, Endothelin A/metabolism , Sodium Chloride, Dietary/metabolism , Time Factors
2.
Phys Rev Lett ; 94(3): 036601, 2005 Jan 28.
Article in English | MEDLINE | ID: mdl-15698298

ABSTRACT

We realize p- and n-type doping of the organic semiconductor zinc-phthalocyanine using a novel strong organic donor. This allows us to demonstrate the first stable and reproducible organic p-n homojunctions. The diodes show very high built-in potentials, attractive, e.g., for organic solar cells. However, the diode characteristics cannot be described by the standard Shockley theory of the p-n junction since the ideality factor strongly increases with decreasing temperature. We show that this behavior can be explained by deviations from the Einstein relation for disordered materials.

3.
J Am Chem Soc ; 123(38): 9436-42, 2001 Sep 26.
Article in English | MEDLINE | ID: mdl-11562227

ABSTRACT

A series of conducting polymers have been prepared through thermal polymerization of transition-metal diimine complexes. The as-polymerized material is electrochemically converted into its formally zerovalent form. Due to the proximity of the half-wave potentials of the formal 1+/0 and 0/1- couples, there is substantial disproportionation of the redox sites at room temperature, resulting in a conductive tervalent mixed-valent material. The redox processes that give rise to this mixed-valent material are predominantly ligand-based, and therefore are highly sensitive to substitution on the ligand periphery. Solution redox chemistry of the monomer can be used to accurately predict the work function of the corresponding zerovalent conducting polymer, which has been verified by ultraviolet photoelectron spectroscopy. Many of these materials have especially low work functions (<3.6 eV) making them appropriate materials to use as cathode materials in organic light-emitting devices (OLEDs). Working examples of tris(8-hydroxyquinoline)aluminum(III)-based OLEDs have been fabricated using one of these polymers as a cathode.

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