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

Exercise training (ExT) has been shown to reduce sympathetic drive during heart failure (HF). The subfornical organ (SFO) is involved in the neural control of sympathetic drive. We hypothesized that an activated SFO contributes to enhanced sympathetic activity in HF. We also postulated that ExT would reduce the activation of the SFO and its contribution to the sympathetic drive during HF. Sprague-Dawley rats were subjected to coronary artery ligation to induce HF. Rats were assigned to ExT for 3-4 wk. Rats with HF had a 2.5-fold increase in FosB-positive cells in the SFO compared with sham-operated rats, and this was normalized by ExT. Microinjection of ANG II (100 pmol) into the SFO resulted in a greater increase in renal sympathetic nerve activity (RSNA), blood pressure, and heart rate in the HF group than in the sham-operated group. These responses were normalized after ExT (change in RSNA: 23 ± 3% vs. 8 ± 2%). ExT also abolished the decrease in RSNA in HF rats after the microinjection of losartan (200 pmol) into the SFO (-21 ± 4% vs. -2 ± 3%). Finally, there was elevated mRNA (5-fold) and protein expression (43%) of ANG II type 1 receptors in the SFO of rats with HF, which were reversed after ExT. These data suggest that the enhanced activity of the SFO by elevated tonic ANG II contributes to the enhanced sympathoexcitation exhibited in HF. The decrease in ANG II type 1 receptor expression in the SFO by ExT may be responsible for reversing the neuronal activation in the SFO and SFO-mediated sympathoexcitation in rats with HF.