Brain and cardiovascular diseases: common neurogenic background of cardiovascular, metabolic and inflammatory diseases

Abstract

In spite of significant progress in pharmacotherapy the incidence of newly diagnosed cases of cardiovascular diseases and cardiovascular morbidity is alarmingly high. Treatment of hypertension or heart failure still remains a serious challenge. Continuous attempts are made to identify the mechanisms that decide about susceptibility to pathogenic factors, and to determine effectiveness of a specific therapeutic approach. Coincidence of cardiovascular diseases with metabolic disorders and obesity has initiated intensive research for their common background. In the recent years increasing attention has been drawn to disproportionately greater number of depressive disorders and susceptibility to stress in patients with coronary artery disease. An opposite relationship, i.e. a greater number of sudden cardiovascular complications in patients with depression, has been also postulated. Progress in functional neuroanatomy and neurochemistry provided new information about the neural network responsible for regulation of cardiovascular functions, metabolism and emotionality in health and under pathological conditions. In this review we will focus on the role of neuromodulators and neurotransmitters engaged in regulation of the cardiovascular system, neuroendocrine and metabolic functions in health and in pathogenesis of cardiovascular diseases and obesity. Among them are classical neurotransmitters (epinephrine and norepinephrine, serotonin, GABA), classical (CRH, vasopressin, neuropeptide Y) and newly discovered (orexins, apelin, leptin IL-1beta, TNF-alpha, ghrelin) neuropeptides, gasotransmitters, eicozanoids, endocannabinoids, and some other compounds involved in regulation of neuroendocrine, sympatho-adrenal and parasympathetic nervous systems. Special attention is drawn to those factors which play a role in immunology and inflammatory processes. Interaction between various neurotransmitter/neuromodulatory systems which may be involved in integration of metabolic and cardiovascular functions is analyzed. The survey gives evidence for significant disturbances in release or action of the same mediators in hypertension heart failure, obesity, diabetes mellitus, metabolic syndrome, starvation, chronic stress, depression and other psychiatric disorders. With regard to the pathogenic background of the cardiovascular diseases especially valuable are the studies showing inappropriate function of angiotensin peptides, vasopressin, CRH, apelin, cytokines and orexins in chronic stress, cardiovascular and metabolic diseases. The studies surveyed in this review suggest that multiple brain mechanisms interact together sharing the same neural circuits responsible for adjustment of function of the cardiovascular system and metabolism to current needs.