title: Angiotensin-(1-7) in the rostral ventrolateral medulla modulates enhanced cardiac sympathetic afferent reflex and sympathetic activation in renovascular hypertensive rats.
abstract: Enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic excitation in hypertension. The aim of the present study was to determine whether angiotensin (Ang)-(1-7) in the rostral ventrolateral medulla (RVLM) modulated the enhanced CSAR and sympathetic activation, and the signaling pathways that mediated these effects in the 2-kidney, 1-clip renovascular hypertension model. Cardiac sympathetic afferent reflex was evaluated using renal sympathetic nerve activity and mean arterial pressure responses to epicardial capsaicin application in anesthetized sinoaortic-denervated and cervical-vagotomized rats. RVLM microinjection of Ang-(1-7) induced greater increases in renal sympathetic nerve activity and mean arterial pressure, and greater enhancement in CSAR in 2-kidney, 1-clip rats than in sham-operated rats, which was blocked by Mas receptor antagonist A-779, adenylyl cyclase inhibitors SQ22536 and MDL-12,330A, and protein kinase A inhibitors rp-adenosine-3',5'-cyclic monophosphorothionate and H-89. Mas receptor expression in RVLM was increased in 2-kidney, 1-clip rats. Treatment with A-779, SQ22536, MDL-12,330A, rp-adenosine-3',5'-cyclic monophosphorothionate, or H-89 in RVLM inhibited CSAR and decreased renal sympathetic nerve activity and mean arterial pressure in 2-kidney, 1-clip rats, whereas cAMP analogue dibutyryl-cAMP had the opposite effects. Ang-(1-7) in RVLM increased, whereas A-779 decreased the cAMP level and the epicardial capsaicin application-induced increases in the cAMP level in RVLM. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and increases the sympathetic outflow and blood pressure via Mas receptor activation. The increased endogenous Ang-(1-7) and Mas receptor activity in RVLM contributes to the enhanced CSAR and sympathetic activation in renovascular hypertension, and the cAMP-protein kinase A pathway is involved in these Ang-(1-7)-mediated effects in the RVLM.
authors: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Peng
authors: P
authors: Li
authors: Hai-Jian
authors: HJ
authors: Sun
authors: Bai-Ping
authors: BP
authors: Cui
authors: Ye-Bo
authors: YB
authors: Zhou
authors: Ying
authors: Y
authors: Han
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects* / Q000503:physiopathology; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D062186:Arterial Pressure / Q000187:drug effects; D017776:Autonomic Pathways / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000503:physiopathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)