Abstract 1590: Exercise Training Modulates the Cardiac Sympathetic Afferent Reflex and Central Oxidative Stress in Heart Failure Rats
The cardiac sympathetic afferent reflex (CSAR) is an excitatory reflex that contributes to the sympatho-excitation in the chronic heart failure (CHF)state. In a previous study we showed that exercise training (EX) normalized the enhanced CSAR in rats with CHF. This was mediated by a down-regulation of the angiotensin II type 1 receptor in the paraventricular nucleus (PVN). In this study, we hypothesized that normalization of the CSAR(capsaicin 0.4 μg in 2μl,epicardial application) following EX (Running on treadmill,15– 60min/day,10–25m/min, 0–10% grade, 3– 4 wk) in CHF rats is due to lower superoxide production in the PVN. EX significantly decreased basal superoxide levels and NAD(P)H-derived superoxide production and increased total superoxide dismutase (SOD) and Mn-SOD activity in the hypothalamus of CHF rats (table⇓, * P<0.05 vs. Sham; # P<0.05 vs. CHF, n=12/group). Using the superoxide-sensitive fluorescence dye, dihydroethidium,the increase in superoxide was mainly confined to the PVN. EX decreased the enhanced CSAR to the level observed in sham rats. This was reversed by intracerebroventricular (icv) infusion of the SOD inhibitor DETC (80 μg/kg, in 10 μl for 10min). Moreover, both the NAD(P)H oxidase inhibitor apocynin (60 μg/kg, in 10 μl for 10min, icv) and the SOD mimetic tempol (80 μg/kg in 10 μl for 10min, icv) completely abolished the enhanced CSAR in untrained CHF rats, but had no effect on EX CHF rats. In conclusion, EX normalized the enhanced CSAR in CHF, which was mediated by lower central oxidative stress related to reduced NAD(P)H oxidase activity and increased SOD activity .