It is well known that chronic heart failure (CHF) is characterized by increased sympathetic outflow and a blunted baroreflex sensitivity. Our previous studies have demonstrated that the enhanced cardiac sympathetic afferent reflex (CSAR) is an important contributor to these autonomic dysfunctions in CHF, and furthermore, the interaction between the CSAR and autonomic dysfunction occurs in the central nervous system. The rostral ventrolateral medulla (RVLM) plays a critical role in the tonic and reflex control of cardiovascular function. The imbalance between Angiotensin II (Ang II) and Ang (1-7) in the periphery and the brain has recently been reported to play an important role in mediating altered cardiovascular function in various disease states. Based on the above evidence, we hypothesize that the RVLM is an important, integrative region involved in the interaction between the enhanced CSAR and autonomic dysfunction (e.g. increased sympathetic outflow and the blunted baroreflex) in CHF, which is mediated by Ang II and/or Ang (1-7) signaling. Therefore, 3 specific aims will be addressed in this proposal. Aim 1: To determine if the RVLM is involved in mediating the enhanced CSAR in CHF; Aim 2: To determine if the enhanced CSAR contributes to abnormalities in Ang II signaling in the RVLM in CHF; Aim 3: To determine if the enhanced CSAR contributes to the imbalance between Ang II and Ang (1-7) signaling in the RVLM in CHF. This proposal will provide new insight into our understanding about the regulation of the neural control of cardiovascular function in CHF. This proposal integrates into the overall theme of our laboratory in potentially providing additional evidence for the central control of autonomic functions in CHF. In addition, this project will provide important evidence concerning the mechanism responsible for the interaction between the CSAR and autonomic function.
|Effective start/end date||07/01/2011 → 06/30/2013|