Angiotensin-(1–7) in the Rostral Ventrolateral Medulla Modulates Enhanced Cardiac Sympathetic Afferent Reflex and Sympathetic Activation in Renovascular Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2013-04, Vol.61 (4), p.820-827
• Main Authors: Li, Peng, Sun, Hai-Jian, Cui, Bai-Ping, Zhou, Ye-Bo, Han, Ying
• Format: Article
• Language: English
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - physiopathology; Angiotensin I - pharmacology; Animals; Antihypertensive Agents - pharmacology; Arterial hypertension. Arterial hypotension; Arterial Pressure - drug effects; Autonomic Pathways - drug effects; Autonomic Pathways - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Disease Models, Animal; Hypertension, Renovascular - drug therapy; Hypertension, Renovascular - physiopathology; Male; Medical sciences; Medulla Oblongata - drug effects; Medulla Oblongata - physiopathology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - physiopathology; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.00191

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.