Effects of exercise training on SFO-mediated sympathoexcitation during chronic heart failure.

Am J Physiol Heart Circ Physiol. 2014 Jan;306(1):H121-31. Llewellyn TL, Sharma NM, Zheng H, Patel KP. “Exercise training (ExT) has been shown to reduce sympathetic drive during heart failure (HF)”. Recently the authors from this laboratory showed that the paraventricular nucleus (PVN) of the hypothalamus was activated in rats with HF and exercise training (EXT) normalized this effect but the mechanisms that mediate the enhanced activation of the PVN are unknown. Subfornical organ (SFO) is a circumventricular organ that lacks blood brain barrier and has been shown to have neuronal connections with the PVN. In the present study, the authors hypothesized that SFO is activated in HF and contributes to the regulation of sympathetic drive in HF. To test this hypothesis, the authors performed several experiments. First, they induced HF in normal SD rats and found these rats had increased neuronal activity in the SFO compared to normal rats. Second, angiotensin II was microinjected in the SFO, which increased renal SNA, blood pressure and heart rate in the HF animals compared to rats without HF. Third, Losartan (AT1 receptor blocker) was microinjected in the SFO to confirm that angiotensin II effects are mediated through AT1 receptor. Losartan decreased RSNA in HF rats. Finally biochemical changes of AT1 receptors in the SFO showed elevated expression in HF rats. Exercise treatment reversed the changes at each experimental condition. These findings suggests that enhanced ang II in the SFO contributes to the activation of SFO and in turn leads to sympathoexcitation in HF and these effects could be reversed by exercise training. - Madhan