TY - JOUR
T1 - AT1 receptor in paraventricular nucleus mediates the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure
AU - Wang, Han Jun
AU - Zhang, Feng
AU - Zhang, Ying
AU - Gao, Xing Ya
AU - Wang, Wei
AU - Zhu, Guo Qing
N1 - Funding Information:
This study was supported by grants from National Natural Science Fund and the Jiangsu Province Department of Education in China.
PY - 2005/8/31
Y1 - 2005/8/31
N2 - Our previous studies have shown that the cardiac sympathetic afferent reflex (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this reflex which was mediated by AT1 receptor. The aim of the present study was to determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were responsible for the enhanced CSAR in rats with coronary ligation-induced chronic heart failure (CHF). Under urethane and α-chloralose anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by epicardial application of bradykinin (BK, 0.04 and 0.4 μg) were determined respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50 nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but had no significant effects in sham-operated rats. AT1 receptor protein in the PVN significantly increased in CHF rats compared with sham-operated rats. These results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT1 receptor in the PVN contributed to the enhanced CSAR in the CHF state.
AB - Our previous studies have shown that the cardiac sympathetic afferent reflex (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this reflex which was mediated by AT1 receptor. The aim of the present study was to determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were responsible for the enhanced CSAR in rats with coronary ligation-induced chronic heart failure (CHF). Under urethane and α-chloralose anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by epicardial application of bradykinin (BK, 0.04 and 0.4 μg) were determined respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50 nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but had no significant effects in sham-operated rats. AT1 receptor protein in the PVN significantly increased in CHF rats compared with sham-operated rats. These results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT1 receptor in the PVN contributed to the enhanced CSAR in the CHF state.
KW - AT receptor
KW - Angiotensin II
KW - Cardiac sympathetic afferent reflex
KW - Chronic heart failure
KW - Paraventricular nucleus
KW - Sympathetic nerve activity
UR - http://www.scopus.com/inward/record.url?scp=24344434546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24344434546&partnerID=8YFLogxK
U2 - 10.1016/j.autneu.2005.07.003
DO - 10.1016/j.autneu.2005.07.003
M3 - Article
C2 - 16099221
AN - SCOPUS:24344434546
SN - 1566-0702
VL - 121
SP - 56
EP - 63
JO - Autonomic Neuroscience: Basic and Clinical
JF - Autonomic Neuroscience: Basic and Clinical
IS - 1-2
ER -