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The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
PURPOSE: Lean hypertension (HTN) is characterized by a mechanistically different HTN when compared to obese HTN. The purpose of this study is to assess whether body phenotype influences blood pressure (BP) responses following both acute and chronic exercise. METHODS: Obese (body mass index (BMI) > 30 kg/m2) and lean (BMI < 25 kg/m2) men with pre-hypertension (PHTN) (systolic BP (SBP) 120 - 139 or diastolic BP (DBP) 80 - 89 mm Hg) were asked to participate in a two-phase trial. Phase 1 assessed differences in post-exercise hypotension between groups in response to an acute exercise bout. Phase 2 consisted of a two-week aerobic exercise intervention at 65-70% of heart rate (HR) max on a cycle ergometer. Primary outcome measures were: brachial BP, central (aortic) BP, cardiac output (CO), and systemic vascular resistance (SVR) measured acutely after one exercise session and following two weeks of training. RESULTS: There were no differences between groups for baseline resting brachial BP, central BP, age, or VO2 peak (all P > 0.05). At rest, obese PHTN had greater CO compared to lean PHTN (6.3 ± 1 vs 4.7 ± 1 L/min-1, P = 0.005) and decreased SVR compared to lean PHTN (1218 ± 263 vs 1606 ± 444 Dyn.s/cm5, P = 0.003). Average 60-minute post-exercise brachial and central SBP reduced by 3 mm Hg in Lean PHTN in response to acute exercise (P < 0.005), while significantly increasing 4 mm Hg for brachial and 3 mm Hg for central SBP (P < 0.05). SVR had a significantly greater reduction following acute exercise in lean PHTN (-223 Dyn·s/cm5) compared to obese PHTN (-75 Dyn·s/cm5, P < 0.001). In lean subjects chronic training reduced brachial BP by 4 mm Hg and central BP by 3 mm Hg but training had no effect on the BP’s in obese subjects. Resting BP reduction in response to training was accompanied by reductions in SVR within lean (-169 Dyn·s/cm5, P < 0.001), while obese experienced increased SVR following training (47 Dyn·s/cm5, P < 0.001). CONCLUSION: Hemodynamic response to both acute and chronic exercise training differ between obese and lean individuals.
ContributorsZeigler, Zachary (Author) / Swan, Pamela (Thesis advisor) / Gaesser, Glenn (Committee member) / Buman, Matthew (Committee member) / Angadi, Siddhartha (Committee member) / Farouk, Mookadam (Committee member) / Arizona State University (Publisher)
Created2016
Description
Cardiovascular disease has long been one of the leading causes of morbidity in the world and places a large burden on the health care system. Exercise has been shown to reduce the risk of developing cardiovascular disease and the risk factors associated with it. Much of the focus of research has been on aerobic exercise modalities and their effect on these risk factors, and less is known in regard to the effect of resistance training. One novel risk factor for cardiovascular disease is arterial stiffness, specifically aortic stiffness. Aortic stiffness can be measured by carotid-femoral pulse wave velocity (PWV) and central pressure characteristics such as central blood pressures and augmentation index. The objective of this study was to assess the effect that two different 12-week long resistance training interventions would have on these measurements in sedentary, overweight and obese men and women (BMI ≥ 25 kg/m2). Twenty-one subjects completed the study and were randomized into one of the following groups: control, a low repetition/high load (LRHL) group which performed 3 sets of 5 repetitions for all exercises, and a high repetition/low load (HRLL) group which performed 3 sets of 15 repetitions for all exercises. Those in the resistance training groups performed full-body exercise routines on 3 nonconsecutive days of the week. Changes in arterial stiffness, central blood pressures, and brachial blood pressures were measured before and after the 12-week intervention period. PWV showed significant group by time interaction (p= 0.024) but upon post hoc testing no significant differences were observed due to the control group confounding (control: 7.6 ± 0.8 vs. 7.1 ± 0.8, LRHL: 6.7 ± 0.5 vs. 6.9 ± 0.5, HRLL: 7.03 ± 0.67 vs. 6.59). No other significant interactions or differences were observed for any of the variables tested. Based on the results of this study a 12-week long resistance intervention training, neither high nor moderate-intensity resistance training, resulted in improvements in indices of vascular stiffness or central and peripheral blood pressures.
ContributorsWeeldreyer, Nathan (Author) / Angadi, Siddhartha (Thesis advisor) / Gaesser, Glenn (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2020