title: Angiotensin-(1-7) enhances the effects of angiotensin II on the cardiac sympathetic afferent reflex and sympathetic activity in rostral ventrolateral medulla in renovascular hypertensive rats.
abstract: Excessive sympathetic activity propels the pathogenesis and progression of organ damage in hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation in hypertension. Given the important role of the renin-angiotensin (Ang) system in regulating sympathetic outflow and cardiovascular activity, the present study aimed to investigate the roles of Ang-(1-7) in Ang II-induced CSAR and the sympathetic activation responses in the rostral ventrolateral medulla (RVLM) of hypertensive rats. The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate the CSAR in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. Both Ang II and Ang-(1-7) in the RVLM caused greater increases in RSNA and MAP in 2K1C rats than in sham-operated (sham) rats and enhanced CSAR independently. RVLM pretreatment with Ang-(1-7) dose dependently augmented the effects of Ang II on RSNA, MAP, and CSAR in 2K1C rats. Mas receptor antagonist A-779 in the RVLM exhibited more powerful inhibitory effects on RSNA, MAP, and CSAR than the Ang II type 1 (AT1) receptor antagonist losartan. The expression of both the AT1 receptor and Mas receptor proteins in the RVLM increased, but neither the Ang II nor Ang-(1-7) levels in the RVLM changed significantly in the 2K1C rats compared with the sham rats. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and sympathetic output not only by itself but also through enhancing the effects of Ang II in renovascular hypertensive rats. Both endogenous Ang-(1-7) and Ang II in the RVLM contribute to the enhanced CSAR and sympathetic activation in renovascular hypertension.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Sun
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: yhancn@njmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
mesh_terms: D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan
keywords: Angiotensin II; angiotensin-(1–7); cardiac sympathetic afferent reflex; hypertension; rostral ventrolateral medulla