Investigation of Hydrogen Peroxide/Reactive Oxygen Species-Related Signaling on Vasoactive Responses in Myogenic Resistance Arteries

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dc.contributor.advisorBraun, Andrew P.
dc.contributor.authorKendrick, Dylan John
dc.contributor.committeememberCole, William C.
dc.contributor.committeememberSlater, Donna M.
dc.contributor.committeememberVon Der Weid, Pierre Yves
dc.date2019-06
dc.date.accessioned2019-04-01T15:16:28Z
dc.date.available2019-04-01T15:16:28Z
dc.date.issued2019-03-28
dc.description.abstractThe study focuses on the investigation of H2O2 and reactive oxygen species as a putative contributor to endothelium-derived hyperpolarization in myogenically-active resistance arteries, and its contribution to the responses evoked by established vasoactive agents. In particular, I hypothesize that H2O2 and/or ROS serve as physiologic, vasoactive agents in myogenically-active resistance arteries in normal tissue and/or in arteries exhibiting endothelial dysfunction (i.e. conditions with reduced NO bioavailability). Using a number of different experimental protocols such as lucigenin molecular assays provided the amount of NADPH-oxidase inhibition in the presence of apocynin, ML171 and VAS2870, where pressure myography experiments showed the response of rat cremaster arteries to external hydrogen peroxide, indicating a role for hydrogen peroxide within the vasculature. Pressure myography experiments also showed the arterial response to the different NADPH-oxidase inhibitors in terms of baseline myogenic tone. Application of apocynin (10µM and 100µM) further constricted the vessels, ML171 resulted in a transient relaxation, with a full relaxation seen with exposure to higher concentrations (0.1µM, 0.3µM, 10µM) of VAS2870. Responses to established vasoactive agents were observed in the presence of the NADPH-oxidase inhibitors, showing reduced responses at ~50% NADPH-oxidase inhibition, with enhanced responses at greater NADPH-oxidase inhibition. The study shows that the three structurally diverse NADPH-oxidase inhibitors differentially affect basal myogenic tone at concentrations (~IC50 values) that produce comparable inhibition of vascular NADPH-oxidase activity.en_US
dc.identifier.citationKendrick, D. J. (2019). Investigation of Hydrogen Peroxide/Reactive Oxygen Species-Related Signaling on Vasoactive Responses in Mammalian Resistance Arteries (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/36331
dc.identifier.urihttp://hdl.handle.net/1880/110127
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectCardiovascularen_US
dc.subjectresistance arteriesen_US
dc.subjectresistance arteriesen_US
dc.subjecthydrogen peroxideen_US
dc.subjectendothelial dysfunctionen_US
dc.subjectNADPH-oxidaseen_US
dc.subject.classificationPhysiologyen_US
dc.subject.classificationPharmacologyen_US
dc.titleInvestigation of Hydrogen Peroxide/Reactive Oxygen Species-Related Signaling on Vasoactive Responses in Myogenic Resistance Arteriesen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Cardiovascular/Respiratory Scienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrue
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