Aerobic exercise regulates synaptic transmission and reactive oxygen species production in the paraventricular nucleus of spontaneously hypertensive rats

Aerobic exercise lowers blood pressure in patients with hypertension, but the underlying mechanisms remain incompletely understood. The hypothalamic paraventricular nucleus (PVN) plays a key role in the control of sympathetic outflow and cardiovascular tone. We examined whether chronic aerobic exercise altered synaptic transmission and reactive oxygen species (ROS) production in the PVN. In the present study, spontaneously hypertensive rats (SHRs) were subjected to exercise training for 8 weeks, five times per week, with Wistar Kyoto (WKY) rats as the cohort control. Miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were recorded from the PVN in ex vivo hypothalamic slice preparations obtained after the last training, and biomarkers of oxidative stress and physical indexes were observed. The mean frequency and amplitude, as well as the rise time and the decay time constant of mIPSCs, significantly decreased in 20-wk-old SHRs compared to WKY 20-wk-old controls. In contrast to mIPSCs, only the mean mEPSC frequency was higher, and there were no other changes in mEPSCs in comparison to the control group. SHRs exhibited higher ROS, 8-OHdG, and MDA; and lower SOD1, SOD2, CAT, Ogg1, and SOD and CAT activity in the PVN. These SHRs also had a significant increase in heart rate, blood pressure and sympathetic nerve activity, and higher levels of norepinephrine (NE). Exercise training ameliorated all these abnormalities, resulting in an increase in the mean frequency, amplitude and kinetics of mIPSCs, accompanied by a decrease in the mean frequency of mEPSCs in the PVN. This study demonstrates that moderate intensity, high frequency exercise training induces a selective enhancement of inhibitory synaptic transmission in the PVN, which may dampen sympathetic activity and reduce blood pressure in hypertension. These changes may be due to antioxidant-related adaptations in the PVNs of SHRs.