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.