title: Heart Failure as a Disruption of Dynamic Circulatory Homeostasis Mediated by the Brain.
abstract: Circulatory homeostasis is associated with interactions between multiple organs, and the disruption of dynamic circulatory homeostasis could be considered as heart failure. The brain is the central unit integrating neural and neurohormonal information from peripheral organs and controlling peripheral organs using the autonomic nervous system. Heart failure is worsened by abnormal sympathoexcitation associated with baroreflex failure and/or chemoreflex activation, and by vagal withdrawal, and autonomic modulation therapies have benefits for heart failure. Recently, we showed that baroreflex failure induces striking volume intolerance independent of left ventricular dysfunction. Many studies have indicated that an overactive renin-angiotensin system, excess oxidative stress and excess inflammation, and/or decreased nitric oxide in the brain cause sympathoexcitation in heart failure. We have demonstrated that angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), which is known as a vasomotor center, causes prominent sympathoexcitation in heart failure model rats. Interestingly, systemic infusion of angiotensin II directly affects brain AT1R with sympathoexcitation and left ventricular diastolic dysfunction. Moreover, we have demonstrated that targeted deletion of AT1R in astrocytes strikingly improved survival with prevention of left ventricular remodeling and sympathoinhibition in myocardial infarction-induced heart failure. From these results, we believe it is possible that AT1R in astrocytes, not in neurons, have a key role in the pathophysiology of heart failure. We would like to propose a novel concept that the brain works as a central processing unit integrating neural and hormonal input, and that the disruption of dynamic circulatory homeostasis mediated by the brain causes heart failure.
authors.affiliation: Collaborative Research Institute of Innovation for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D012084:Renin-Angiotensin System / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*