Central regulation of body fluid homeostasis

Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na(+) concentration ([Na(+)]) in body fluids is maintained at 135–145 mM and is broadly conserved among terrestrial animals. Homeostatic osmoregulation by Na(+) is vital for life because severe hyper- or hypotonicity elicits irreversible organ damage and lethal neurological trauma. To achieve “body fluid homeostasis” or “Na homeostasis”, the brain continuously monitors [Na(+)] in body fluids and controls water/salt intake and water/salt excretion by the kidneys. These physiological functions are primarily regulated based on information on [Na(+)] and relevant circulating hormones, such as angiotensin II, aldosterone, and vasopressin. In this review, we discuss sensing mechanisms for [Na(+)] and hormones in the brain that control water/salt intake behaviors, together with the responsible sensors (receptors) and relevant neural pathways. We also describe mechanisms in the brain by which [Na(+)] increases in body fluids activate the sympathetic neural activity leading to hypertension.