Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Oxidative stress induced by reactive oxygen species has been strongly associated with many neurodegenerative diseases (NDDs) and many medicinal plant-derived products have been reported to exert potent antioxidant properties. Sutherlandia frutescens (SF) and Carpobrotus edulis (CE) are two indigenous South African plants with known anti-inflammatory, anti-bacterial, antioxidant and anti-cancer properties. However, the neuroprotective effects of SF and CE have not been extensively studied. Aims: This study was done to investigate the neuroprotective potentials of S. frutescens and C. edulis aqueous extracts on hydrogen peroxide (H2O2)-induced toxicity in an SH-SY5Y neuroblastoma cellular model of oxidative stress injury. Methods: The maximum non-toxic dose (MNTD) of SF and CE against SH-SY5Y cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Thereafter, the cells were exposed to 250 μM H2O2 for 3 hours before treatment with the determined MNTDs of SF and CE extracts respectively and the effects of the treatments on caspase-9 protease activity, intracellular ROS levels, mitochondrial membrane permeability (MMP), nitric oxide (NO) activity, intracellular calcium activity and endogenous antioxidant activity in SH-SY5Y cells was evalaluated using caspase activity kits, DCFH-DA assay, rhodamine 123 fluorescent dye, Griess reagent, Fluo-4 direct calcium reagent, Hoechst staining dye, Superoxide dismutase (SOD) colorimetric and Catalase (CAT) assays, respectively.

O peróxido de benzoíla, produto de interação do peróxido de sódio com cloreto de benzoíla, é um poderoso agente antibacteriano de amplo espectro com ação queratolítica, comedolítica, descamativa, antipruriginosa e desengordurante, além de também ser um potente agente oxidante, que reage com materiais orgânicos rompendo as membranas celulares de inúmeros agentes patogênicos. Em virtude de suas características, o peróxido de benzoíla é utilizado como produto de eleição como adjuvante no tratamento de sarnas (dermodicidoses), desqueratinizações, complexo seborréico, piodermites, foliculites superficiais, impetigo e piodermite de dobras. Neste projeto é abordado o desenvolvimento e validação de um método indicador de estabilidade do fármaco peróxido de benzoíla, cujo objetivo é ser utilizado como ferramenta para a identificação e doseamento de maneira precisa e exata dos produtos de degradação desconhecidos formados, a partir de variados ambientes de acondicionamento estressantes, nos quais o medicamento possa ser eventualmente submetido durante o seu prazo de vida de prateleira. O método analítico proposto foi validado conforme os requerimentos vigentes da ANVISA e se baseia na técnica de cromatografia líquida de alta eficiência (CLAE) para doseamento do princípio ativo e seus produtos de degradação, em uma única corrida analítica, o que permite determiná-los simultaneamente, e portanto é adequado para utilização durante o estudo de estabilidade acelerado e de longa duração, além de metodologia indicadora de estabilidade.Durante o estudo de degradação forçada foram geradas uma série de \"picos\" desconhecidos inerentes ao fármaco, especialmente nas condições de aquecimento, hidrólise em meios ácido e alcalino, e fotólise. Entretanto, durante o estudo foram investigados aqueles originados a partir desta última, uma vez a posologia da preparação medicamentosa estudada é via tópica, pois se trata da forma farmacêutica semi-sólida gel. Para avaliação dos produtos de degradação gerados durante a fotólise foi utilizada a cromatografia líquida com detecção por espectrometria de massas, onde o fármaco foi ionizado na forma positiva (+) através da técnica Electrospray ionization (ESI+), a qual permitiu a proposição da estrutura molecular da substância gerada, a partir da provável perda do grupamento alquil ou aldeído, justificando assim a razão massa carga 199,1 u.m.a. / Benzoyl peroxide , the produced by interaction of sodium peroxide with Benzoyl chloride is a powerful antibacterial agent with keratolytic , comedolytic , scaly , antipruritic and degreasing action, as well as being a powerful oxidizing agent that reacts with organic materials disrupting the membrane cell of many pathogens agents . Due to its characteristics, benzoyl peroxide is used as the main choice in the treatment of scabies, seborrhea complex, pyoderma, superficial folliculitis, impetigo and pyoderma folds. This project addresses the development and validation of an indicator stability method for benzoyl peroxide, which is intended to be used as a tool for the identification and accurate and preciously determination of unknown degradation products formed from various stressful environments, in which the API may eventually be submitted during the period of shelf life. The proposed analytical method was validated according to the applicable/current requirements of ANVISA and it is based on the technique of high performance liquid chromatography (HPLC) assay for the active ingredient and its degradation products in a single analytical run, allowing dosing them simultaneously, and thus it is suitable for use during accelerated and long term stability studies and as stability indicating method. During the forced degradation study many unknown \"peaks\" inherent to drug were generate, especially under heating, acid and alkaline hydrolysis, beyond photolysis conditions. However, throughout this study were investigated that obtained from the photolysis, since the sample preparation are applied topically because it is semi - solid dosage gel form. To evaluate the degradation products generated during photolysis were used liquid chromatography with detection by mass spectrometry, where the drug was ionized in the positive (+) form by technical Electrospray ionization (ESI+) technique, which allowed the proposition of the molecular structure substance generated from the probable loss of the alkyl or aldehyde grouping , thus justifying the mass/charge ratio 199.1 amu.

O presente trabalho visa o estudo da eletrossíntese de H2O2 a partir da reação de redução de oxigênio (RRO) utilizando carbono Printex 6L modificado com óxidos binários compostos de nióbio, molibdênio e paládio, síntetizados pelo método dos precursores poliméricos. A análise dos materiais preparados foi feita a partir de experimentos de análise termogravimétrica (do inglês, TGA), fluorescência de raios X (FRX) e também de difração de raios X (DRX). As temperaturas de síntese foram escolhidas a partir dos resultados de TGA e tendo como temperatura máxima de 400 °C. As análises dos espectros de emissão de FRX mostraram a eficiência na incorporação dos materiais na matriz de carbono. Experimentos de DRX mostraram a presença de fases cristalinas de MoO2 e Nb2 O5 e PdO, e em comparação aos resultados da técnica de voltametria cíclica, existem pares redox que podem ser associados as transições dos metais nos estados de oxidação de +4 e +5, para molibdênio e nióbio, respectivamente e do estado +2 para o paládio. Nos experimentos de voltametria de varredura linear pode-se observar a tendência de maior geração de H2O2 pelo material com teor de 1% NbMo quando comparado com o carbono Printex 6L, de modo que foram calculadas as eficiências de geração de H2O2 , obtendo um resultado de 55,5% para o modificador de 1% NbMo comparado com 47,4% para o Printex 6L, e também de número de elétrons envolvidos na reação com um valor de 2,9 para o material de 1% e 3,1 para o carbono Printex. As análises das curvas de Koutechy-Levich confirmam os resultados anteriores. Análises em condições reduzidas na síntese orgânica corroboraram a melhor eficiência do material de 1% para o material com nióbio e molibdênio e revelaram a também a melhora eletrocatalítica do carbono quando incorporado com óxidos mistos de nióbio e paládio, sendo o melhor resultado expresso no material contendo 5% de nióbio e paládio, na proporção molar de 95 para 5% de cada elemento, respectivamente. / The present work aim the electrosynthesis study of H2O2 from the reduction reaction of oxygen (RRO) using carbon Printex 6L modified with binary oxides composed of niobium, molybdenum and palladium, synthetized by precursors method. The analyses of prepared compounds were made from thermogravimetric analyses (TGA) as well as x-ray fluorescence (XRF) and x-ray diffraction (XRD). The synthesis temperature was chosen by TGA results and having a maximum temperature of 400oC. The emission spectrum analysis from XRF showed the efficiency of materials incorporation in carbon matrix. DRX experiments showed the presence of crystalline phases of MoO2, Nb2O5 and PdO, and in comparison to the cyclic voltammetry technique results, there are redox pairs which can be associated to the transition of the metals in oxidation states of +4 and +5, to molybdenum and niobium, respectively, and state of +2 for palladium. In the experiments linear sweep voltammetry, it can be observed that the tendency of higher H2O2 generation by the material with 1% of NbMo content when it is compared to the Printex 6L carbon, so that were calculated the efficiency of H2O2 generation, obtaining a result of 55,5% for the 1% modifier in comparison with 47,4% for the Printex carbon, as well as the number of electrons involved in the reaction with a value of 2,9 to the 1% material and 3,1 to the Printex carbon. The analysis of Koutechy-Levich curves, confirm the previous results. Analysis under reduced conditions in the organic synthesis corroborates to greater efficiency of 1% material to the material with niobium and molybdenum and they also revealed the electrocatalytic improvement of carbon when it is incorporated with mixed oxide of niobium and palladium, being the best result expressed in the material containing 5% of niobium and palladium, in the molar proportion of 95 to 5% of each element, respectively

Vanadium is commonly used as an agent to make tools rust-resistant. As a transition metal, it can be used as a catalyst due to its ability to change oxidation states. VO(HEDTA)-1, a complex of the vanadyl ion, VO2+ and HEDTA (N-(2-Hydroxyethyl)ethylenediamine-N,N’,N’-triacetic acid) was readily formed. This complex containing vanadium in the +4 oxidation state was reacted with hydrogen peroxide to form a vanadate complex. This vanadate complex was formed as a first step in simulating the vanadate(V)-dependent haloperoxidases in marine algae, a yet uncharacterized reaction. Electron absorption spectroscopy (UV-Vis) was used to observe the oxidation of V(IV) in the complex to V(V) through the color change of the complex from blue to yellow. This color change was observed through the formation of a peak at 450nm. By changing the initial concentrations of VO(HEDTA)-1, hydrogen peroxide, and hydronium ion, the change in absorbance at 450nm during the first minutes of the reaction was correlated with time to determine the initial rates for each reactant. Using this method, a rate equation for the reaction was determined. The rate of reaction was determined to be first order with respected to VO(HEDTA)-1 and H2O2, and 1/2 order with respect to H+. This half-order indicates that the hydronium ion is engaged in a reversible reaction. The involvement of hydroxyl radicals produced by the reaction, as shown by the effect of free radical scavengers to inhibit the reaction was also studied.

Orientador: Luciano Tavares Angelo Cintra / Coorientador: André Luiz Fraga Briso / Banca: Denise Pedrini Ostini / Banca: Renata Oliveira Samuel / Resumo: Novos produtos estão sendo desenvolvidos com o propósito de atenuar os efeitos dos compostos utilizados em procedimentos clareadores. O objetivo do presente estudo foi avaliar in vivo o potencial terapêutico do gel de Biosilicato® (BS) sobre o tecido pulpar de molares de ratos Wistar, por meio das análises histológica e imunoistoquímica, assim como analisar in vitro, a penetração do H2O2 e a eficácia clareadora em dentes bovinos. Para isso, este estudo foi dividido em 2 partes. Parte 1: Segmento in vivo: 50 hemi-maxilas de 25 ratos foram divididas aleatoriamente em 5 grupos (n=10): Controle- não recebeu qualquer tratamento; CLA- recebeu 30 min do gel clareador H2O2 35%; BS-CLA- recebeu 20 min do gel de BS, seguido de 30 min do H2O2 35%; CLA+BS- recebeu 30 min de uma mistura do H2O2 35% com o gel BS (1:1); CLA+H2O- recebeu 30 min de uma mistura do H2O2 35% com água destilada (1:1). Após 2 dias, os animais foram mortos e as hemi-maxilas separadas para análise histológica em H.E. Foram atribuídos escores à inflamação e os dados submetidos aos testes de Kruskal-Wallis e Dunn e teste de Mann-Whitney (p<0,05). Segmento in vitro: 50 discos de dentes bovinos foram acoplados em câmaras pulpares artificiais, e divididos em 5 grupos (n=10) que receberam os mesmos tratamentos que o segmento in vivo. A penetração do H2O2 por esmalte e dentina foi quantificada baseada na reação deste com o corante violeta leucocristal. A alteração de cor foi analisada pelo sistema CIELab, nos períodos: ant... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: New products are being developed with the purpose of mitigating the effects of the compounds used in bleaching procedures. The objective of the present study was to evaluate in vivo the therapeutic potential of Biosilicate® (BS) gel on the pulp tissue of Wistar rats by means of histological and immunohistochemical analysis, as well as to analyze in vitro, the penetration of H2O2 and bleaching efficiency in bovine teeth. For this, this study was divided into 2 parts. Part 1: In vivo segment: 50 hemi-maxilla of 25 rats were randomly divided into 5 groups (n = 10): Control- received no treatment; CLA- received 30 min of the 35% H2O2 bleaching gel; BS-CLA- received 20 min of BS gel, followed by 30 min of 35% H2O2; CLA+BS- received 30 min of a mixture of 35% H2O2 with the BS gel (1:1); CLA+H2O- received 30 min of a mixture of 35% H2O2 with distilled water (1:1). After 2 days, the animals were killed and the hemi-maxils separated for histological analysis in H.E. Inflammation scores and data submitted to the Kruskal-Wallis and Dunn tests and Mann-Whitney test (p<0.05) were assigned. Segment in vitro: 50 discs of bovine teeth were coupled in artificial pulp chambers, and divided into 5 groups (n=10) that received the same treatments as the in vivo segment. The penetration of H2O2 by enamel and dentin was quantified based on the reaction of this with the leucocrystal violet dye. The color change was analyzed by the CIELab system, in the periods: before the bleaching session - (T0), i... (Complete abstract click electronic access below) / Mestre

Probiotics are living organisms which exert a beneficial health effect when consumed in sufficient numbers. Consumer interest in probiotics has increased dramatically in recent years prompting an increase in production and development of functional foods. One major problem is the decreased viability of probiotic bacteria during functional food production and storage and subsequent digestion due to environmental stresses. The most common probiotic strains belong to the genus Lactobacillus or Bifidobacterium. Due to the anaerobic nature of these bacteria, they lack the required defense mechanisms for oxidative stress inherent in aerobic microorganisms. This study examined the oxidative stress responses of six strains of Bifidobacterium, which are commonly used as probiotics in functional foods.The first phase of the study investigated the innate and inducible hydrogen peroxide (H2O2) stress response of Bifidobacterium longum strains NCC2705 and D2957, Bifidobacterium longum ssp. infantis ATCC 15697, and Bifidobacterium animalis ssp. lactis strains BL-04, DSM10140 and RH-1. Strains were screened for survival at increasing concentrations of H2O2 and lethal and sublethal concentrations were determined for each. In the second phase, B. animalis ssp. lactis strains BL-04 and DSM10140 and B. longum strains NCC2705 and D2957 were treated with a sublethal H2O2 concentration and RNA samples were collected for transcriptome analysis after 5 min and either 20 or 60 min. Statistical analysis was performed to identify genes that increased or decreased in expression during H2O2 treatment compared to control cells.Results showed that survival was species and strain dependent and that strains which naturally survived higher H2O2 concentrations had a larger number of differentially expressed genes early on during H2O2 exposure. Some of the protective genetic systems that were activated during H2O2 stress are mechanisms which perform basic cellular functions under normal conditions such as deoxuynucleotide synthesis. Under stress conditions, these systems can be used to detoxify oxidative free radicals. Also a number of genes involved in sugar transport and energy production for the cell showed increased expression, which reveals the increased energy needs of the cells during oxidative stress.During testing, it was found that two B. animalis ssp. lactis strains, BL-04 and DSM10140, had differing levels of survival and gene expression during H2O2 exposure despite having almost identical genome sequences. It was determined that one possible cause of the differences was a genetic deletion in a gene that allows the cell to incorporate extracellular fatty acids into the cell membrane instead of synthesizing them.Results from this project have increased the understanding of oxidative stress responses in bifidobacteria and highlighted possible methods to increase bacterial survival during food manufacture, storage, and human digestion.

"October, 2005" / Coursework / Bibliography: leaves 97-105. / xvi, 136 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D.Clin.Dent.)--University of Adelaide, Dental School (Endodontics), 2005

Recently, metal nanoparticles have attracted the attention of researchers in several fields of study due to their high surface area and other unique properties. Using metal nanoparticles as a component of an in situ chemical oxidation (ISCO) system is emerging and hence very little information is available. In this research, nano zero valent iron (nZVI) particles and iron-based bimetallic zero valent nanoparticles (BZVNs) were employed to activate some common peroxygens (hydrogen peroxide (H2O2), persulfate (S2O82-), and peroxymonosulfate (HSO5-)) to degrade hazardous organic compounds. Aqueous and soil slurry batch systems were used along with a one-dimensional physical model. The results from the aqueous batch systems showed that nZVI is a promising activator for S2O82- compared to other conventional iron activators (e.g., granular-ZVI and Fe2+). For example, the initial trichloroethylene (TCE) reaction rate by nZVI activated S2O82- was 1.11 x 10-4 M L-1 min-1 compared to an initial reaction rate of 6.25 x 10-5 M L-1 min-1, 5.18 x 10-6 M L-1 min-1, and 1.8 x 10-7 M L-1 min-1 for Fe2+ activated S2O82-, granular-ZVI activated S2O82-, and non-activated S2O82-, respectively. However, the surfaces of nZVI particles were passivated quickly following exposure to S2O82-, causing the reaction rate to reduce to a magnitude representative of an un-activated S2O82- system. An iron-sulfate (FeSO4) complex was formed on the surfaces of the nZVI particles following exposure to S2O82- compared to the iron oxyhydroxide (FeOOH) layer that was present on fresh nZVI surfaces. BZVNs showed better treatment effectiveness than nZVI particles as activators for H2O2, S2O82-, and HSO5-. For example, the TCE reaction rate constant for nano-Ag-Fe0 activated H2O2 was 9 to 18 fold higher than that for nZVI activated H2O2. Of the nine different BZVNs investigated as activators, the greatest TCE degradation was achieved by nano-Pd-Fe0 and nano-Zn-Fe0 activated S2O82- system, nano-Co-Fe0 activated HSO5- system, and nano-Ag-Fe0 activated H2O2 system. For all of these systems, an increase in the dosage of nanoparticles and peroxygens increased TCE degradation. The activated H2O2 system showed a lower TCE degradation rate compared to either the activated S2O82- or the activated HSO5- systems, suggesting that a bridged group complex is formed between the activators and H2O2. The dissolved TCE concentration remaining in the soil slurry batch systems after using the nano-Pd-Fe0 activated S2O82- system was two to three fold higher than that in an aqueous batch system. Furthermore, for five different aquifer materials used, the higher mass of aquifer materials the lower the TCE degradation, indicating that the aquifer materials compete with a target organic compound in the presence of activated S2O82-. A linear relationship was observed between the organic carbon (OC) content and the initial TCE decomposition rate. Although there is no direct evidence of the effect of OC on the treatment system, it is suggested that the OC may result in scavenging the generated free radicals or by directly consuming persulfate. In the one-dimensional physical model systems, bimetallic nanoparticles were mobile in a non-geological porous medium and relatively immobile in a geological porous medium. In the non-geological porous medium, we found that adding a second metal (e.g., Pd) to nano-Fe0 particles significantly improved their functionality and performance (e.g., mobility and suspension). For example, the results from mobility experiments using columns packed with glass beads showed that the effluent iron concentration was <6 % of the influent iron concentration for the nano-Fe0 particles, while it was ~100 % for the nano-Pd-Fe0 particles. In the geological porous medium, based on visual inspection, nano-Pd-Fe0 particles could not travel more than a few centimeters into columns packed with CFB Borden sand, and no iron was detected in the effluent. To overcome the delivery issue in porous media, nano-Pd-Fe0 particles were injected to create a zone of activation to activate S2O82- for the treatment of TCE source zone. However, we found that the TCE mass destruction was only 9 % higher in the nano-Pd-Fe0 activated S2O82- system compared to the non-activated S2O82- system as revealed by the effluent chloride concentration. In addition, the activation zone composed of nano-Pd-Fe0 particles was rapidly deactivated after exposure to persulfate as visually observed by color change, indicating that the longevity of the activation zone is limited. This research effort provides a contribution to the field of ISCO by evaluating the potential utility and applicability of a new class of activators for some common peroxygens.

It is well established that hypertension decreases endothelium-dependent vasomotor function, partially by excessive generation and reduced scavenging of reactive oxygen species (ROS). Nevertheless, at appropriate levels, some ROS can act as signaling molecules in the vasculature and contribute to endothelium-dependent dilation. Recent evidence in healthy resistance arteries suggests that the ROS species hydrogen peroxide (H2O2) acts as an endogenous endothelium-dependent dilator through a non-nitric oxide, non-prostaglandin (3NP) pathway. The aim of this study was to investigate the role of endogenous H2O2 in 3NP-mediated endothelium-dependent dilation of rat mesenteric arteries, and the changes that occur in these vessels with essential hypertension. 18-20wk old male spontaneously hypertensive rats (SHR; n=24) had an elevated systolic blood pressure of 198±6mmHg compared to 93±4mmHg (p<0.001) in the age matched normotensive Wistar-Kyoto rat (WKY; n=22). Isolated mesenteric arteries were preconstricted with norepinephrine (NEPI), followed by exposure to increasing doses of the endothelium-dependent dilator acetylcholine (ACh), which revealed vasomotor dysfunction in the SHR (maximal dilation: WKY: 94.8±1.3% vs. SHR: 75.2±2.9%, p<0.001). Incubation of the vessels with the non-specific cyclooxygenase (COX) inhibitor indomethacin (INDO) restored the ACh response in the SHR to the level of the WKY control (area under the curve: WKY: 354.6±8.6 vs. SHR INDO: 350.2±12.2, p>0.05) indicating that the release of constrictory prostaglandins from COX contribute to endothelial vasomotor dysfunction. Co-incubation of vessels with INDO and the nitric oxide synthase inhibitor Nω-nitro-L-arginine (LN) inhibited dilation in SHR (46.2±4.8%, p<0.001) but not in WKY (98.3±1.5%, p>0.05), indicating an elevated 3NP component in WKY over SHR. Further co-incubation with the H2O2 scavenger catalase (CAT), LN, and INDO inhibited the 3NP component to a greater extent in SHR (29.7±3.1%, p=0.062) than in WKY (91.6±2.5%, p<0.05). The responses of SHR and WKY mesenteric arteries to the endothelium-independent dilator sodium nitroprusside, the receptor-mediated constrictor NEPI, and the electrochemical constrictor KCl were no different between LN INDO and CAT LN INDO conditions. These data suggest that endogenous H2O2 has a greater role in mediating endothelium-dependent dilation in the mesenteric resistance arteries of SHR. Interestingly, in SHR, co-incubation with LN INDO improved dilation over LN alone (46.2±4.8% vs 23.3±3.2±, p=0.001), and CAT LN INDO decreased dilation from LN INDO to a similar extent, suggesting that COX-inhibition could be a source of H2O2 for endogenous vasodilation. Western blotting revealed a 54% increase in COX-1 protein expression in the SHR mesenteric arteries (WKY: 1.00±0.18 (n=9) vs. SHR: 1.54±0.17 (n=13), p<0.05), but no difference in the expression of the pro-oxidant enzyme p47phox, and the anti-oxidant enzymes CAT, SOD-1, and SOD-2. Administration of exogenous H2O2 to NEPI preconstricted mesenteric arteries revealed a dose-dependent dilation that was no different between SHR and WKY, and incubation of isolated WKY and SHR mesenteric arteries with CAT reduced the accumulation of H2O2 to a similar extent, as assessed by the H2O2-specific fluorescent dye Amplex Red. In conclusion, endogenous H2O2 is a vasodilator in the mesenteric arteries of SHR and WKY rats in the absence of nitric oxide and prostaglandins. In the SHR, COX-1 inhibition may allow endogenous H2O2 to become bioavailable for vasodilation. This study is the first to show a role for endogenous H2O2 in maintaining endothelium-dependent dilation in hypertensive rat resistance arteries, and provides evidence to support a role for COX-1-inhibition in the increased availability of H2O2 for dilation.

It is well established that hypertension decreases endothelium-dependent vasomotor function, partially by excessive generation and reduced scavenging of reactive oxygen species (ROS). Nevertheless, at appropriate levels, some ROS can act as signaling molecules in the vasculature and contribute to endothelium-dependent dilation. Recent evidence in healthy resistance arteries suggests that the ROS species hydrogen peroxide (H2O2) acts as an endogenous endothelium-dependent dilator through a non-nitric oxide, non-prostaglandin (3NP) pathway. The aim of this study was to investigate the role of endogenous H2O2 in 3NP-mediated endothelium-dependent dilation of rat mesenteric arteries, and the changes that occur in these vessels with essential hypertension. 18-20wk old male spontaneously hypertensive rats (SHR; n=24) had an elevated systolic blood pressure of 198±6mmHg compared to 93±4mmHg (p<0.001) in the age matched normotensive Wistar-Kyoto rat (WKY; n=22). Isolated mesenteric arteries were preconstricted with norepinephrine (NEPI), followed by exposure to increasing doses of the endothelium-dependent dilator acetylcholine (ACh), which revealed vasomotor dysfunction in the SHR (maximal dilation: WKY: 94.8±1.3% vs. SHR: 75.2±2.9%, p<0.001). Incubation of the vessels with the non-specific cyclooxygenase (COX) inhibitor indomethacin (INDO) restored the ACh response in the SHR to the level of the WKY control (area under the curve: WKY: 354.6±8.6 vs. SHR INDO: 350.2±12.2, p>0.05) indicating that the release of constrictory prostaglandins from COX contribute to endothelial vasomotor dysfunction. Co-incubation of vessels with INDO and the nitric oxide synthase inhibitor Nω-nitro-L-arginine (LN) inhibited dilation in SHR (46.2±4.8%, p<0.001) but not in WKY (98.3±1.5%, p>0.05), indicating an elevated 3NP component in WKY over SHR. Further co-incubation with the H2O2 scavenger catalase (CAT), LN, and INDO inhibited the 3NP component to a greater extent in SHR (29.7±3.1%, p=0.062) than in WKY (91.6±2.5%, p<0.05). The responses of SHR and WKY mesenteric arteries to the endothelium-independent dilator sodium nitroprusside, the receptor-mediated constrictor NEPI, and the electrochemical constrictor KCl were no different between LN INDO and CAT LN INDO conditions. These data suggest that endogenous H2O2 has a greater role in mediating endothelium-dependent dilation in the mesenteric resistance arteries of SHR. Interestingly, in SHR, co-incubation with LN INDO improved dilation over LN alone (46.2±4.8% vs 23.3±3.2±, p=0.001), and CAT LN INDO decreased dilation from LN INDO to a similar extent, suggesting that COX-inhibition could be a source of H2O2 for endogenous vasodilation. Western blotting revealed a 54% increase in COX-1 protein expression in the SHR mesenteric arteries (WKY: 1.00±0.18 (n=9) vs. SHR: 1.54±0.17 (n=13), p<0.05), but no difference in the expression of the pro-oxidant enzyme p47phox, and the anti-oxidant enzymes CAT, SOD-1, and SOD-2. Administration of exogenous H2O2 to NEPI preconstricted mesenteric arteries revealed a dose-dependent dilation that was no different between SHR and WKY, and incubation of isolated WKY and SHR mesenteric arteries with CAT reduced the accumulation of H2O2 to a similar extent, as assessed by the H2O2-specific fluorescent dye Amplex Red. In conclusion, endogenous H2O2 is a vasodilator in the mesenteric arteries of SHR and WKY rats in the absence of nitric oxide and prostaglandins. In the SHR, COX-1 inhibition may allow endogenous H2O2 to become bioavailable for vasodilation. This study is the first to show a role for endogenous H2O2 in maintaining endothelium-dependent dilation in hypertensive rat resistance arteries, and provides evidence to support a role for COX-1-inhibition in the increased availability of H2O2 for dilation.