Central AT1 receptors are involved in the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure.

Abstract

The purpose of this study was to determine if the cardiac sympathetic afferent reflex (CSAR) was augmented in rats with coronary ligation-induced chronic heart failure (CHF), and if central angiotensin II (ANG II) was involved in this enhancement. Under alpha-chloralose and urethane anesthesia, mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized rats. An intracerebroventricular cannula was implanted. The CSAR was examined by epicardial application of bradykinin (BK, 0.04 and 0.4 microg in 2.0 microl) or capsaicin (0.04 and 0.4 microg in 2.0 microl) to the anterior and posterior wall of the left ventricle. The CSAR evoked by BK or capsaicin was augmented in rats with CHF. In sham rats, there was no significant difference of the CSAR induced by BK or capsaicin between anterior and posterior epicardial application. However, in rats with CHF, the CSAR induced by BK (0.04 microg) to anterior epicardial application was blunted compared with posterior application. Intracerebroventricular injection of losartan (500 nmol) normalized the enhanced CSAR in rats with CHF, but had no significant effects on the CSAR in sham rats. However, intravenous application of the same dose of losartan only decreased the baseline MAP, but did not alter baseline RSNA or the CSAR in sham or CHF rats. Pre-treatment with epicardial application of lidocaine to the anterior wall abolished the CSAR evoked by application of BK or capsaicin but had no effects on the CSAR evoked by epicardial application of BK or capsaicin to the posterior wall. These results suggest that the CSAR induced by epicardial application of BK and capsaicin is enhanced in the rats with CHF, and the enhanced CSAR is mediated by central AT(1) receptors.