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

The 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.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Medicine – Cardiovascular/Respiratory Science

Grantor dc:publisher.institution

Cumming School of Medicine

Year dc:date.issued

2019

Author dc:creator

• Kendrick, Dylan John

Advisor dc:contributor.advisor

• Braun, Andrew P.

Committee members dc:contributor.committeemember

• Cole, William C.
• Slater, Donna M.
• Von Der Weid, Pierre Yves

• Cardiovascular
• resistance arteries
• hydrogen peroxide
• endothelial dysfunction
• NADPH-oxidase

Statement dc:rights

• University 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.

Language dc:language.iso

en

DOI

http://dx.doi.org/10.11575/PRISM/36331

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/110127