2019 Volume 56 Issue 4 Pages 211-215
Heart failure is a disruption of the circulatory homeostasis regulated by brain interaction with multiple organs. The brain understands the circulatory homeostasis from neural and hormonal inputs, and determines efferent sympathetic output. In this system, the brain works as a central processing unit integrating neural information and hormonal factors. We have demonstrated the mechanisms of the brain in heart failure. Angiotensin II receptor type 1 (AT1R)-induced oxidative stress and inflammation in the vasomotor center cause heart failure via sympathoexcitation. Targeted deletion of AT1R in astrocytes, which are more abundant than neurons and are connected with neurons and the vascular system, remarkably improved survival with prevention of left ventricular (LV) remodeling and sympathoinhibition. In addition, the central arc of the baroreflex (from the carotid sinus pressure to the sympathetic output) fails in heart failure, and baroreflex failure induces marked volume intolerance independent of LV dysfunction worsening the renal pressure-diuresis relationship. On the basis of these results, we consider that the brain is a novel therapeutic target in heart failure via sympathoinhibition.
