title: AT1 receptor in paraventricular nucleus mediates the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure.
abstract: 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 alpha-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 microg) 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.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Han-Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xing-Ya
authors.initials: XY
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D002216:Captopril; D001920:Bradykinin