Cardiac sympathetic afferent stimulation inhibits the arterial baroreflex in heart failure at the level of the nucleus tractus solitarius by an angiotensin II mechanism

Abstract

The enhanced cardiac sympathetic afferent reflex (CSAR) has been suggested to contribute to increased sympathetic outflow and blunted baroreflex via a central angiotensin II (Ang II) mechanism in chronic heart failure (CHF). This work was designed to determine the Ang II mechanism in the nucleus tractus solitarius (NTS) underlying the interaction between the baroreflex and the CSAR using extracellular recording in rats with CHF. CHF was produced by coronary artery ligation. Of 38 NTS cells tested for barosensitivity by elevation of arterial pressure, 28 were recorded in CHF rats and 10 were tested in sham rats. CSAR activation by epicardial application of capsaicin (0.4 μg) attenuated the barosensitivity of 12 NTS neurons by 86.2 ± 9.3% and this was significantly greater in CHF rats than in sham rats (65.7 ± 6.3%). In 8 cells from CHF rats, tonic inhibition of CSAR by epicardial lidocaine (6 μl) improved the barosensitivity of NTS neurons by 42.8 ± 5.9 %. In the remaining 8 cells from CHF rats, intravenous injection of the Ang II AT1 receptor antagonist losartan (2 mg/kg) not only sensitized the barosensitivity by 83.1 ± 7.2% but also reversed the inhibitory effect of CSAR activation on barosensitivity (−84.7 ± 9.6 vs. −12.5 ± 4.8 %). In conclusion, these data suggest that the NTS plays an important role in mediating the blunting of baroreflex by CSAR activation via an AT1 receptor dependent mechanism in CHF.