The difficullty to distinguish between sheep and goats is a well-known problem in archaeology and osteology. Distinguishing sheep and goats in archaeological animal remains takes time and time is often limited for osteologists. Because of this difficulty osteologists and archaeozoologists often use the term sheep/goat or ”ovicaprids” in their analytical reports. But even if the term sheep/goat comprise both species, this is often not the case when archaeologists and osteologists interpret and present archaeological findings. Sheep usually dominates in the interpretations and is often seen as a more important animal than goats which ultimately lead to false representations of the species and their relation to humans in the past. Zeder and Lapham (2010) have gathered criterias for post-cranial bone elements which show a high degree of reliability in osteological species determination between sheep and goats. However, when working on archaeological remains you do not know if the evaluation is done correctly.      In this thesis, the use of ocular osteological methods from by Zeder and Lapham (2010) are combined with genetical analyzis of selected sheep and goat bones from an archaeological assemblage in order to evaluate how well these osteological methods perform and assess which criterias on the bone elements can be seen as reliable when used to distinguish between the species. According to the results, only three criterias of a total of 21 criterias are seen as reliable. It is also apparent that previous osteological experience is relevant for successfully distinguish between sheep and goat with these methods. However, several criterias show tendencies towards reliability and are probably affected by the small sample set for each bone element, few osteological analysts, and the fact that all genetically analyzed bones resulted in sheep.

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.

Microfluidic chips have drawn great attention and interest due to their broad applications in chemical, biological and biomedical fields. These kinds of miniaturized devices offer many advantages over the traditional analysis instruments, such as reduced cost, shortened time, increased throughput, improved integration/automation/portability, etc. However, the concept of integrating multiple labs on a single chip to perform micro total analysis hasn’t been realized yet because of the lack of fundamental knowledge and systematic design of each component, especially for some particular applications. A thorough understanding and grasp of the basic physical phenomenon is the theoretical basis to develop functional devices to utilize them. In this study, we intend to investigate the electrokinetic fluid flow and coherent species transport processes in microchannels, and then try to effectively control them for designing related lab-on-a-chip devices. Rather than expensive experiments, numerical studies are performed to simulate the different processes involved in various electrokinetic chip applications. In the theoretical models, applied potential field, flow field and species concentration field are considered and corresponding governing equations with initial/boundary conditions are numerically solved by computational fluid dynamics techniques. The flow field is obtained by the developed SIMPLE algorithm and a slip-wall velocity boundary condition is applied in simulating electroosmotic flow. Grid independence tests and convergence studies are performed to ensure economic computation with adequate accuracy and stability. For every application with typical channel layout, parametric studies are performed to investigate different effects through the controlling parameters linked to them. For surface patterning or microfabrication using laminar flows, various operational parameters are investigated to explore the optimized configurations for multi-stream flow and mass transport control in cross-linked microchannels. Through a series of numerical simulations, it is found that applied potentials, electroosmotic mobilities of solutions and channel dimensions have significant effects on the flow and mass transport after converging in the intersection of channel network. Diffusion coefficient has less influence than the other parameters due to the presence of high Peclet number for such applications. For the microwashing with two different electrolyte solutions, a three-dimensional model is numerically solved to reveal the flow structure change. In a straight microchannel with a rectangle cross section, KCl solution and LaCl3 solution are mainly employed for tests. Displacement processes between two solutions in both orders are tested and analyzed. The observed flow structures such as back flow in channel center and distortion of plug-like velocity profile are noticed and discussed. The distortion of the flow field results from the induced pressure gradient, which is due to the non-uniformity of electroosmotic mobilities and electrical conductivities of two replaced solutions. The bigger difference two solutions have in chemical properties, the stronger effects on flow they have. Effect of applied potential field strength is also studied and the approximate linear influences are concluded. Finally, the unsteady on-chip sample injection and separation processes involved in microchip capillary electrophoresis are studied. Species’ electrophoretic migration effect is included and the theoretical model is non-dimensionalized in a unique manner with the key fundamental parameters: the Re Sci , species’ non-dimensional electrophoretic mobility and applied potentials. The species transport characteristics are revealed numerically and well understood for future effective control and innovative chip design. Species front movement during injection and sample plug development in separation are examined with diffusion effect; results include concentration profiles and contour plots over a range of injection and separation time. The influence of i Re Sc which characterizes the relative role of convection versus diffusion is examined over the commonly encountered range and the diffusion effect is found to have an essentially negligible effect. Through three species, the electrophoretic mobilities difference is demonstrated to be the reason for separation. Real-time monitoring of different species’ movements is performed for injection guidance.

In order to assess the benefit or toxicity of chromium in dietary supplements, trivalent chromium and hexavalent chromium must be measured and verified with mass balance (sum of both species equaling total chromium). This is necessary because dietary supplements report trivalent chromium, an essential trace element, as an ingredient, but hexavalent chromium, a toxic carcinogen, may also be present. Because trivalent chromium is stable in acidic conditions and hexavalent chromium in alkaline conditions, interconversions between species occur and increase the difficulty of quantification. Therefore, EPA Method 3060A was first performed to extract hexavalent chromium. Then, EPA Method 3052 was performed on the residue to digest the remaining trivalent chromium. Speciated Isotope Dilution Mass Spectrometry (SIDMS) with Ion-Exchange Chromatography-Inductively Coupled Plasma-Mass Spectrometry (IC-ICP-MS) was used to account for interconversions as well as determination of trivalent and hexavalent chromium concentrations in the studied samples. Mass balance indicated that the analyzed supplements contained hexavalent chromium ranging from 0 to 16% of the total chromium content. / Bayer School of Natural and Environmental Sciences; / Environmental Science and Management (ESM) / MS; / Thesis;

Dictyostelium discoideum serves as an ideal system to study social evolution because of the social stage of its lifecycle, where individuals aggregate to build a multicellular structure. However, much of its basic biology remains unknown and this limits its utility. I used three separate projects to fill these gaps. In my first project, I examined how speciation and genetic diversity affects kin discrimination using a related dictyostelid, Polysphondylium violaceum . I sequenced the ribosomal DNA of 90 clones of P. violaceum and found that P. violaceum is split into several morphologically identical groups. When allowed to cooperate in pairwise mixes, I found that some clones cooperated with others in their group, but in mixes between groups, clones did not cooperate. For my second project, I looked at whether D. discoideum has sex in natural populations. While sex has been observed in laboratory clones of D. discoideum , it is unclear whether sex occurs in natural populations, and sex can influence the evolution of traits. I used a dataset of microsatellites in 24 clones of D. discoideum to look for a decrease in linkage disequilibrium as a molecular sign of sex. Linkage disequilibrium is higher between physically close loci than between loci on different chromosomes. From this, I conclude that D. discoideum undergoes recombination in nature. Lastly, I used the genome sequence of D. discoideum to look at large scale patterns of evolution. Mutations tend to be biased towards A/T from G/C so, on average, mutations should lower the nucleotide content of sequences. The removal of these mutations, purifying selection, should preserve nucleotide content. I used the genomes of D. discoideum and Plasmodium falciparum identify classes of sequences that should be under different amounts of purifying selection and compared their nucleotide contents. In all cases, those sequences under more purifying selection had higher GC contents than sequences under less purifying selection. Looking at relative nucleotide content may thus serve as an indicator purifying selection. These three studies add insight on how cooperation works in dictyostelids as well as adding an understanding of how traits, social and otherwise, would evolve in this system.

With a   growing human population, cities keep growing worldwide altering ecosystem   and thereby affecting the species living in these areas. Most studies of   urbanization and its effect on ecosystem have been conducted in the western   world and little is known about its effect in the neotropical part of the   world. I examined effects of fragment size, vegetation structure and   connectivity of urban green areas on bird species richness, mean abundance,   diversity and biomass in La Paz, Bolivia. Additionally, the effects of   different disturbance variables on bird community were evaluated. In total,   36 bird species were found in 24 fragment of varying size, connectivity and   level of disturbance. Bird species richness decreased with increasing   disturbance while connectivity and fragment size did not contribute   significantly to explain the variation in species richness at count point scale (p&gt;0.005, multiple linear regression). At fragment   scale, however, species richness increased with fragment sizes,   which has been shown in other studies from neotrophical regions. Variation in   abundance, diversity or biomass could not be explained by connectivity,   fragment size or disturbance.     Furthermore, coverage of construction had a negative effect on species   richness while coverage of bushes and coverage of herbs were negatively   related to biomass and diversity, respectively. The composition of bird   species differed with size and disturbance of the fragments, so that more   omnivorous and granivorous species such as Zonotrichia capensis, Turdus chiguanco and Zenaida auriculata, were present in areas highly affected by human activities. Larger fragments,   less affected by human presence held a larger proportion of insectivorous   species.

No previous studies have been conducted on elementary school in Sweden about children`s thoughts about the first animals on earth. The work takes up the children`s ideas of the first animals and the difference between girls and boys knowledge. The purpose of this work was to determine if student`s views are consistent with the science know today. In the interview, five girls and five boys participated. Mankind is asking where it all began, today we know that the first life arose for 4 billion years ago and it was from the water. Students think it was a small animal which then developed into another animal through a natural process.

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.

Microfluidic chips have drawn great attention and interest due to their broad applications in chemical, biological and biomedical fields. These kinds of miniaturized devices offer many advantages over the traditional analysis instruments, such as reduced cost, shortened time, increased throughput, improved integration/automation/portability, etc. However, the concept of integrating multiple labs on a single chip to perform micro total analysis hasn’t been realized yet because of the lack of fundamental knowledge and systematic design of each component, especially for some particular applications. A thorough understanding and grasp of the basic physical phenomenon is the theoretical basis to develop functional devices to utilize them. In this study, we intend to investigate the electrokinetic fluid flow and coherent species transport processes in microchannels, and then try to effectively control them for designing related lab-on-a-chip devices. Rather than expensive experiments, numerical studies are performed to simulate the different processes involved in various electrokinetic chip applications. In the theoretical models, applied potential field, flow field and species concentration field are considered and corresponding governing equations with initial/boundary conditions are numerically solved by computational fluid dynamics techniques. The flow field is obtained by the developed SIMPLE algorithm and a slip-wall velocity boundary condition is applied in simulating electroosmotic flow. Grid independence tests and convergence studies are performed to ensure economic computation with adequate accuracy and stability. For every application with typical channel layout, parametric studies are performed to investigate different effects through the controlling parameters linked to them. For surface patterning or microfabrication using laminar flows, various operational parameters are investigated to explore the optimized configurations for multi-stream flow and mass transport control in cross-linked microchannels. Through a series of numerical simulations, it is found that applied potentials, electroosmotic mobilities of solutions and channel dimensions have significant effects on the flow and mass transport after converging in the intersection of channel network. Diffusion coefficient has less influence than the other parameters due to the presence of high Peclet number for such applications. For the microwashing with two different electrolyte solutions, a three-dimensional model is numerically solved to reveal the flow structure change. In a straight microchannel with a rectangle cross section, KCl solution and LaCl3 solution are mainly employed for tests. Displacement processes between two solutions in both orders are tested and analyzed. The observed flow structures such as back flow in channel center and distortion of plug-like velocity profile are noticed and discussed. The distortion of the flow field results from the induced pressure gradient, which is due to the non-uniformity of electroosmotic mobilities and electrical conductivities of two replaced solutions. The bigger difference two solutions have in chemical properties, the stronger effects on flow they have. Effect of applied potential field strength is also studied and the approximate linear influences are concluded. Finally, the unsteady on-chip sample injection and separation processes involved in microchip capillary electrophoresis are studied. Species’ electrophoretic migration effect is included and the theoretical model is non-dimensionalized in a unique manner with the key fundamental parameters: the Re Sci , species’ non-dimensional electrophoretic mobility and applied potentials. The species transport characteristics are revealed numerically and well understood for future effective control and innovative chip design. Species front movement during injection and sample plug development in separation are examined with diffusion effect; results include concentration profiles and contour plots over a range of injection and separation time. The influence of i Re Sc which characterizes the relative role of convection versus diffusion is examined over the commonly encountered range and the diffusion effect is found to have an essentially negligible effect. Through three species, the electrophoretic mobilities difference is demonstrated to be the reason for separation. Real-time monitoring of different species’ movements is performed for injection guidance.

Glutathione (GSH), a 3-amino acid compound is ubiquitously expressed in eukaryotic cells and is the most abundant low molecular weight thiol. The importance of GSH is highlighted by its multitude of effects. Within the vascular wall GSH plays a crucial role as an intracellular antioxidant and it possess the ability to act as a signalling intermediate and store for nitric oxide (NO). The importance of NO and its role in vascular wall homeostasis is well recognized. Within the coronary circulation, NO is the primary dilator of many of the large arteries and the smaller arterioles. In addition to controlling coronary vascular tone, the importance of NO is highlighted by its antithrombotic, antihypertrophic, and antriproliferative effects. During instances of cardiovascular disease and normal aging, increases in the production of reactive oxygen species occur. A portion of the deleterious vascular effects of reactive oxygen species are believed to be due to reduction in NO bioavailability as a result of increased ROS-mediated destruction of NO. Altered GSH production in humans has been demonstrated to reduce endothelial function. Conversely, supplementation with GSH augments endothelium-dependent dilation. The mechanisms by which these alterations in GSH influence vasomotor function have not been resolved. The purpose of the studies within this thesis was to examine the impact of chronic and acute GSH modulations on coronary vascular resistance (CVR) and endothelium dependent dilation. In all experiments vascular reactivity was assessed in the isolated perfused rat heart. The advantage of this technique is that it allows the global coronary vasomotor functioning to be examined. Hearts were allowed to stabilize for 30 minutes to allow for the development of spontaneous coronary vascular resistance, followed by a bradykinin (BK) dose-response curve to assess endothelium-dependent dilation. The coronary circulation was then maximally dilated using an endothelium-independent agonist. In all cases BK-mediated dilation is expressed as a percentage of the endothelium-independent dilation. Chapter 2 of this document examines the chronic nature of GSH depletion and examines whether GSH depletion augments the influence of natural aging. Animals (mean age 33 and 65 weeks) were randomized to receive L-Buthionine-(S,R)-sulphoximine (BSO) in the tap water in order to inhibit GSH synthesis, or regular tap water (normal controls). Following 10 days of BSO treatment, ventricular GSH content was reduced in the BSO group compared to the control (0.182±0.021 vs 2.022±0.084 nmol/mg wet weight, p<0.05) and there was increased ventricular H2O2 content (1.345±0.176 vs 0.877±0.123 pmol/µg PRO, p<0.05). Baseline CVR was significantly reduced in the older animals compared to the adult animals (3.92±0.34 vs 4.76±0.20 and 3.67±0.24 vs 5.12±0.37 mmHg/ml×min-1 in the control and BSO treated groups, p<0.05). Conversely, in the presence of LNAME there was a significant increase in CVR in the adult BSO group (14.15±0.99, p<0.05) compared to all other groups. In the absence of LNAME, maximal dilation (percent endothelium-independent response) was reduced in the older animals compared to the adult animals (77±10.3% vs 95.0±1.0% for older and adult control and 92.7±4.5% vs 98.6±0.6% for the older and adult BSO, main effect of age). In the presence of LNAME the adult BSO group had a significantly reduced sensitivity (EC50) compared to all other groups (-7.39±0.09 Log M, p<0.05). Additionally, adult BSO treated animals had an increase in eNOS protein content. These results demonstrate that chronic thiol depletion resulted in an increased reliance on NO in the adult BSO group only. In chapter 3 the beneficial effects of GSH supplementation on BK mediated dilation were examined. Acute GSH was administered in the perfusate at either 0 (control) or with 10 µM for 2 reasons, 1) this concentration does not reduce basal coronary vascular resistance, allowing for a similar baseline CVR across conditions and 2) the 10 µM concentration is a physiologically relevant concentration of plasma/extracellular fluid GSH. The sensitivity to the endothelial agonist bradykinin was enhanced in the presence of GSH (-8.70±0.16 vs -7.94±0.06 LogM, p<0.01). The GSH effect was not dependent on NO production or utilization by soluble guanylate cyclase (sGC) as the enhanced dilation in the GSH group was maintained despite NOS (LNAME) and/or sGC inhibition. When the hearts were supplemented with a ROS scavenger TEMPOL, enhanced dilation was seen in the control group, but was not further enhanced in the GSH group. The requirement for ROS was best demonstrated when both the CON and GSH groups were supplemented with both TEMPOL and LNAME. This condition resulted in similar sensitivity (-7.76±0.19 vs -7.75±0.17 LogM, p>0.05) and area under the curve (182.33±12.70 vs 170±13.86, p>0.05) between GSH and CON. Thus, it was concluded that the effects of GSH administration requires the presence of ROS and exerts its effect in the microvasculature. The study presented in chapter 4 examined the effects of acute thiol modulation (depletion) on CVR and endothelium-dependent dilation. Previous reports have suggested that a reduction in intracellular GSH causes impaired NO production, and functional data support this contention. However, a majority of the data regarding the effects of thiol manipulation are from endothelial-removed vessels. The following agents were used to reduce GSH: the glutathione reductase inhibitor, BCNU; the thiol oxidizing agent, diamide; the thiol conjugating agent, ethacrynic acid (EA); and a thioredoxin inhibitor (CDNB). Preliminary data revealed that only CDNB (11.46±0.71 mmHg/ml×min-1) and EA (8.61±0.36 mmHg/ml×min-1) caused an elevation in CVR compared to the control (6.73±0.24 mmHg/ml×min-1). Conversely, Diamide and BCNU did not significantly affect baseline CVR, or the BK mediated responses. In the presence of EA, there was an overall blunting of the BK-response curve as observed by reduced EC50 (-7.85±0.07 Log M) and maximal dilation (90.8±1.8 %, percent endothelium-independent dilation) compared to the control group (-8.42±0.08 Log M and 97.7±1.6%). In the presence of CDNB the maximal dilation was 74.4±1.9% and the EC50 was -8.83±0.28 Log M. In addition to altering BK mediated responses, acute thiol depletion with all agents resulted in an increased minimal CVR with significant increases observed in the presence of CDNB and EA. There was a significant correlation with GSH:GSSG ratio and baseline (-0.547, p<0.05) and minimal CVR (r=-0.581, p<0.05). This study demonstrates that modulation of the GSH:GSSG ratio using a variety of agents with diverse mechanisms elicits differential responses within the vasculature. Specifically conjugation of GSH and inhibition of thioredoxin significantly alters BK mediated response, where as BCNU and dimaide did not. These results suggest that a modulation in the GSH:GSSG ratio impairs endothelium-dependent dilation and alters total dilatory capacity (baseline-minimal CVR) and thus may have implications for adequate tissue perfusion. Across all studies there was significant correlation between GSH and GSSG with both baseline and minimal CVR. Therefore it is likely that changes in overall glutathione content plays a role in determining baseline and minimal coronary vascular resistance. These results demonstrate the complexity that manipulations of GSH have on both CVR and endothelium-dependent dilation, and provide mechanistic insight into how changes in GSH alter coronary vascular resistance and endothelium-dependent dilation.