Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

In this study, we investigated the effect of the ruthenium complex [Ru(terpy)(bdq)NO+](3+) (TERPY) on the arterial pressure from renal hypertensive 2 kidney-1 clip (2K-1C) rats, which was compared with sodium nitroprusside (SNP). The most interesting finding was that the intravenous bolus injection of TERPY (2.5, 5.0, 7 mg/kg) had a dose-dependent hypotensive effect only in 2K-1C rats. On the other hand, SNP (35 and 70 mu g/kg) presented a similar hypotensive effect in both normotensive (2K) and 2K-1C although the effect of 70 mu g/kg was >35 mu g/kg. The injection of the nonselective NO-synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) increased the arterial pressure in 2K and 2K-1C rats with a similar magnitude. After infusion of L-NAME, the hypotensive effect induced by TERPY and SNP was potentiated in both 2K and in 2K-1C rats. The administration of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl increased the hypotensive effect induced by TERPY or SNP in both 2K and 2K-1C rats. The hypotensive effect induced by TERPY was longer than that produced by SNP. Taken together, our results show that the TERPY has a long-lasting hypotensive effect, which has a dose dependence and higher magnitude in 2K-1C compared with in 2K rats. In comparison with SNP, TERPY is less potent in inducing arterial pressure fall, but it presents a much longer hypotensive effect.

Opto-electrical properties of single layer flexible electroluminescence device with ruthenium complex

In this work, a ruthenium hexafluorophosphate complex, [Ru(bpy)(3)](PF6)(2) in poly(methylmethacrylate) (PMMA) was employed to build a single layer light electrochemical cell on indium tin oxide polyester flexible substrate. The electroluminescence spectrum features a relatively broad band peaked near 625 run, with CIE (x,y) color coordinates of (0.61,0.39). The driving voltage is only 3 V, and for the maximum electrical current of 10 mA the brightness reaches 1 cd/m(2). Regarding the useful application of the device, its opto-electrical behavior under mechanical strain was studied considering the central curvature. In these situations, both electrical characterization in DC mode and luminance were analyzed. (C) 2007 Elsevier B.V. All rights reserved.

Development and characterization of light-emitting diodes (LEDs) based on ruthenium complex single layer for transparent displays

In this work, two ruthenium complexes, [Ru(bpy)(3)](PF6)(2) and [Ru(ph2phcn)(3)](PF6)(2) in poly(inethylinethacrylate) matrix were employed to build single-layer light-emitting electrochemical cells by spin coating on indium tin oxide substrate. In both cases the electroluminescence spectra exhibit a relatively broad band with maxima near to 625 rim and CIE (x, y) color coordinates of (0.64, 0.36), which are comparable with the photoluminescence data in the same medium. The best result was obtained with the [Ru(bpy)(3)](PF6)(2) device where the optical output power approaches 10 mu W at the band maximum with a wall-plug efficiency higher than 0.03%. The lowest driving voltage is about 4 V for an electrical current of 20 mA. (c) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cis-trans isomerization in the syntheses of ruthenium cyclam complexes with nitric oxide

The cis to trans isomerizations during the syntheses of trans-[Ru(NO)(OH)(cyclam)](PF6)(2), from cis-[RuCl2 (cyclam)]Cl, and [Ru(NO)Cl(cyclam)] (PF6)(2), from cis-[RuCl2(dmso)(4)], are reported. The novel trans-[Ru(NO) (OH)(cyclam)](PF6)(2) complex was characterized by X-ray crystallography and vibrational infrared and nuclear magnetic resonance spectroscopies. The Ru-N-O bond angle (176.75 degrees) and v( NO) (1835 cm(-1)) suggest a nitrosonium character for this hydroxo complex. The crystal and molecular structure of trans-[Ru(NO)Cl(cyclam)] (ClO4)(2)center dot 2 H2O is also reported. Results presented here support the cis-trans isomerization observed for the first time with ruthenium cyclam complexes. (C) 2011 Elsevier B.V. All rights reserved.

Deconvolution of the EPR spectra of vanadium oxide nanotubes

In this work we report results of continuous wave (CW) electron paramagnetic resonance (EPR) spectroscopy of vanadium oxide nanotubes. The observed EPR spectra are composed of a weak well-resolved spectrum of isolated V4+ ions on top of an intense and broad structure-less line shape, attributed to spin-spin exchanged V4+ clusters. With the purpose to deconvolute the structured weak spectrum from the composed broad line, a new approach based on the Krylov basis diagonalization method (KBDM) is introduced. It is based on the discrimination between broad and sharp components with respect to a selectable threshold and can be executed with few adjustable parameters, without the need of a priori information on the shape and structure of the lines. This makes the method advantageous with respect to other procedures and suitable for fast and routine spectral analysis, which, in conjunction with simulation techniques based on the spin Hamiltonian parameters, can provide a full characterization of the EPR spectrum. Results demonstrate and characterize the coexistence of two V4+ species in the nanotubes and show good progress toward the goal of obtaining high fidelity deconvoluted spectra from complex signals with overlapping broader line shapes. (C) 2012 Elsevier Inc. All rights reserved.

Chemical mechanism of controlled nitric oxide release from trans-[RuCl([15]aneN(4))NO](PF6)(2) as a vasorelaxant agent

The nitrosyl ruthenium complex, trans-[RuCl([15]aneN(4))NO](PF6)(2), ([15]aneN(4) = 1,4,8,12-tetraazacyclopentadecane), exhibits vasorelaxation characteristics attributed to its nitric oxide release properties. The observed in vitro and in vivo vasodilation is dependent on noradrenaline concentration. We report here the chemical mechanism of the reaction between noradrenaline and trans-[RuCl([15]aneN(4))NO](PF6)(2) in aqueous phosphate buffer solution at pH 7.40. NO measurement by NO-sensor electrode, cyclic voltammetry, (PNMR)-P-31 and HPLC analysis were used to investigate the reduction process as the fundamental step for NO release characteristic of trans-[RuCl([15]aneN(4))NO](PF6)(2). A supramolecular species containing HPO4 (2-) as a bridging group between noradrenaline and trans-[RuCl([15]aneN(4))NO](PF6)(2) is suggested as an intermediate prior to the reduction of the nitrosyl ruthenium complex.

Interaction among nitric oxide (NO)-related genes in migraine susceptibility

The pathogenic mechanisms involved in migraine are complex and not completely clarified. Because there is evidence for the involvement of nitric oxide (NO) in migraine pathophysiology, candidate gene approaches focusing on genes affecting the endothelial function have been studied including the genes encoding endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and vascular endothelial growth factor (VEGF). However, investigations on gene-gene interactions are warranted to better elucidate the genetic basis of migraine. This study aimed at characterizing interactions among nine clinically relevant polymorphisms in eNOS (T-786C/rs2070744, the 27 bp VNTR in intron 4, the Glu298Asp/rs1799983, and two additional tagSNPs rs3918226 and rs743506), iNOS (C(-1026)A/rs2779249 and G2087A/rs2297518), and VEGF (C(-2578)A/rs699947 and G(-634)C/rs2010963) in migraine patients and control group. Genotypes were determined by real-time polymerase chain reaction using the Taqman(A (R)) allele discrimination assays or PCR and fragment separation by electrophoresis in 99 healthy women without migraine (control group) and in 150 women with migraine divided into two groups: 107 with migraine without aura and 43 with aura. The multifactor dimensionality reduction method was used to detect and characterize gene-gene interactions. We found a significant interaction between eNOS rs743506 and iNOS 2087G/A polymorphisms in migraine patients compared to control group (P < 0.05), suggesting that this combination affect the susceptibility to migraine. Further studies are needed to determine the molecular mechanisms explaining this interaction.

Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting NF-kappa B and upregulating endothelial nitric oxide synthase

de Souza ACCP, Volpini RA, Shimizu MH, Sanches TR, Camara NOS, Semedo P, Rodrigues CE, Seguro AC, Andrade L. Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting nuclear factor-kappa B and upregulating endothelial nitric oxide synthase. Am J Physiol Renal Physiol 302: F1045-F1054, 2012. First published January 11, 2012; doi:10.1152/ajprenal.00148.2011.-The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-kappa B activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP + EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-L-arginine methyl ester (L-NAME) simultaneously with EPO administration (CLP + EPO + L-NAME). A fifth group (CLP + EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP + EPO rats presented significantly higher inulin clearance than did CLP and CLP + EPO + L-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP + EPO rats; and inulin clearance was significantly higher in CLP + EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP + EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-alpha activation, NF-kappa B activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-kappa B downregulation.

Inducible nitric oxide synthase haplotype associated with migraine and aura

Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C-1026 A-rs2779249 and G2087A-rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman (R) allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P < 0.05). No other significant differences in the alleles or genotypes distributions were found (P > 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C-1026 A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.

Release of NO from a nitrosyl ruthenium complex through oxidation of mitochondrial NADH and effects on mitochondria

Nitrosyl ruthenium complexes are promising NO donor agents with numerous advantages for the biologic applications of NO. We have characterized the NO release from the nitrosyl ruthenium complex [Ru(NO2)(bpy)(2)(4-pic)](+) (I) and the reactive oxygen/nitrogen species (ROS/RNS)-mediated NO actions on isolated rat liver mitochondria. The results indicated that oxidation of mitochondrial NADH promotes NO release from (I) in a manner mediated by NO2 formation (at neutral pH) as in mammalian cells, followed by an oxygen atom transfer mechanism (OAT). The NO released from (I) uncoupled mitochondria at low concentrations/incubation times and inhibited the respiratory chain at high concentrations/incubation times. In the presence of ROS generated by mitochondria NO gave rise to peroxynitrite, which, in turn, inhibited the respiratory chain and oxidized membrane protein-thiols to elicit a Ca2+-independent mitochondrial permeability transition; this process was only partially inhibited by cyclosporine-A, almost fully inhibited by the thiol reagent N-ethylmaleimide (NEM) and fully inhibited by the NO scavenger 2-(4-carboxyphenyl)-4,45,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). These actions correlated with the release of cytochrome c from isolated mitochondria as detected by Western blotting analysis. These events, typically involved in cell necrosis and/or apoptosis denote a potential specific action of (I) and analogs against tumor cells via mitochondria-mediated processes. (C) 2012 Elsevier Inc. All rights reserved.