Brain Oxidative Stress Contributes To The Cardiac Dysfunction Of Angina

Objective: The present study was undertaken to investigate the effect of brain oxidative stress on the pathogenesis of angina. The NADPH oxidase inhibitor APO decreases the levels of oxidative stress in the paraventricular nucleus and improves cardiac function in angina rats.Methods and Results: Adult male Sprage-Dawley rats underwent left anterior descending coronary artery ligation to induce angina or sham surgery (SHAM). Rats were implanted with intracerebroventricular (ICV) cannulae and treated with APO (60μg/3min), an NADPH oxidase inhibitor, or vehicle (VEH) for 10 minutes. At the end of the study, left ventricular (LV) function was measured by hemodynamics and rats were sacrificed, and brain was collected for measurement of the expression of gp91^phox using immunohistochemistry. Heart and lung tissues were also harvested, wet lung weight and right ventricular (RV) weight, with respect to body weight (BW), were measured as indices of pulmonary congestion and right ventricular remodeling, two indices of the severity of angina. Angina rats induced significantly increases in the expression of gp91^phox in the paraventricular nucleus (PVN) of hypothalamus compared with sham rats. In contrast, ICV treatment with APO attenuated the expression of gp91^phox in the PVN compared with VEH-treated angina rats. ICV treatment with APO also reduced lung/BW radio and RV/BW radio, decreased LV end-diastolic pressure with increased maximum rate of left ventricular pressure rise (+dp/dt_max) and peak rate of left ventricular pressure fall (-dp/dt_max).Conclusion: These findings suggest that the brain oxidative stress increases in angina rats and inhibitor of brain NADPH oxidase reduces the levels of oxidative stress which can attenuate cardiac dysfunction. Objective: The present study was undertaken to investigate the effect of brain TNF-αon the sympathetic nerve activity in diabetic rats.Methods: Normal adult male Sprage-Dawley rats (200±50)g were fed with high fat and sugar diet for 4 weeks following by injection of streptozotocin to establish the models. Rats were implanted with paraventricular nucleus cannulae and treated with PTX (10μg/h), a phosphodiesterase inhibitor, or vehicle for 4 weeks. Rats were randomly divided into four groups:SHAM+VEH, SHAM+PTX, DM+VEH, DM+PTX. Immunohistochemisty method were applied to detect the expression of TNF-αin the PVN of hypothalamus, renal sympathetic nerve activity (RSNA) was recorded by electrophysiological recording.Results:①C ompared with sham group, diabetes rats induced significantly increases in TNF-αin the PVN of hypothalamus, PVN treatment with PTX attenuated TNF-αexpression in the PVN compared with VEH-treated diabetes rats;②C ompared with sham group, diabetes rats had augmented renal sympathetic nerve activity. In contrast, PVN treatment with PTX also reduced sympathetic nerve activity.Conclusion: Brain TNF-αin the PVN plays an important role on the renal sympathetic nerve activity. It may be of pathogenetic significance in diabetes mellitus.