Publication Date

2013

Document Type

Thesis

Committee Members

Nadja Grobe (Committee Member), Michal Kraszpulski (Committee Member), Roberta Pohlman (Advisor)

Degree Name

Master of Science (MS)

Abstract

Stress is a stimulus that causes an often abrupt but always large change in autonomic activity and hormone secretion. Angiotensin II (AngII) is one of the main neurohormonal mediators that are stimulated by stress. AngII mediates most of its relevant biological effects via AngII type1 receptor (AT1R) activation. Stress increases tissue and circulating levels of Ang II which contributes to stimulation of adrenal AT1R, mediating stressinduced hormone release. Ang II through the activation of AT1R not only elevates blood pressure but also has a patho-physiological relevance in cardiac remodeling. The goal of this study was to assess the influence of AT1 subtype a receptor (AT1aR) on adrenal and cardiac function during chronic swim stress. Adult male AT1a knockout (KO) and wild type (WT) mice (n= 6 per group) were used; groups were exercise KO (KOEX) and exercise WT (WTEX) and control KO and WT. Exercise paradigm was swimming, 1 hour 3d/wk for 7 weeks. Urine and plasma corticosterone (CORT) were measured by radioimmunoassay. Urinary catecholamines were measured using high pressure liquid chromatography with electrochemical detection. Cardiac function was assessed by echocardiography (Echo). Results showed that plasma CORT was lower in KOEX and WTEX as compared to control groups (3 fold decreases). Urinary CORT was used to iv show the dynamic response to exercise stress. Urinary CORT decreased in KOEX after 2 hour from the swimming session compared to the WTEX. These data also showed that KOEX had lower urinary CORT at baseline as compared to the baseline in the WTEX. Urinary catecholamines results indicate that there were no significant differences in Norepinephrine and Epinephrine responses between the KOEX and WTEX. Distance and Velocity significantly increased in KOEX as compared to WTEX. Echo showed a higher ejection fraction (EF %) in KOEX (75%) vs. WTEX (55 %). Assessment of mitral valve function showed a higher A-wave velocity in KOEX as compared to WTEX. AT1a deficient mice showed improved cardiac response and reduced adrenal stress response to chronic exercise. In conclusion, AT1aR is an important mediator of stress induced cardiac dysfunction during exercise training.

Page Count

104

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2013

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