Life Sciences Commons^™

Reactive Oxygen Species And The Regulation Of Cerebral Vascular Myogenic Tone, Neil Mazumdar

Electronic Thesis and Dissertation Repository

The myogenic response refers to the intrinsic ability of arteries to constrict to elevated pressure, developing “tone”. The underlying mechanism has yet to be elucidated but recent evidence suggests that the angiotensin II type 1 receptor (AT1R) is a key mechanosensor, linking intravascular pressure to tone development. One intriguing aspect of this receptor is its ability to activate NADPH oxidase (Nox), an enzyme responsible for the production of reactive oxygen species (ROS). The goal of this study was to ascertain the role of Nox in myogenic tone development. Isolated rat cerebral arteries were mounted in a myograph, pressurized to 60mmHg …

Role Of Rac1 In Myocardial Tnf-Alpha Expression In Sepsis, Ting Zhang

Electronic Thesis and Dissertation Repository

Tumor necrosis factor-a (TNF-alpha) is a pro-inflammatory cytokine and its high levels of expression in the heart leads to cardiac dysfunction in sepsis. However, the underlying molecular mechanisms of regulating myocardial TNF-alpha expression are not fully understood. The aim of this thesis was to investigate the role of Rac1 in myocardial TNF-alpha expression and cardiac dysfunction during sepsis. Studies were performed using cultured neonatal cardiomyocytes and a mouse model of endotoxemia.

PI3K-mediated Rac1 activation is required for induction of TNF-alpha mRNA and protein expression in cardiomyocytes and cardiac dysfunction during endotoxemia. Rac1 promotes TNF-alpha mRNA expression via NADPH oxidase/ERK1/2 and …