Neurochemical Circuits Subserving Fluid Balance and Baroreflex: A Role for Serotonin, Oxytocin, and Gonadal Steroids

Abstract

Changes in body water/sodium balance are tightly controlled by the central nervous system (CNS) to avoid abnormal cardiovascular function and the development of pathological states. Every time there is a disturbance in extracellular sodium concentration or body sodium content, there is also a change in extracellular fluid volume and, depending on its magnitude, this can be associated with an adjustment in arterial blood pressure (BP). The process of sensory integration takes place in different nuclei, with diverse phenotypes and at different levels of the CNS. To control those several changes, the CNS receives continuous input about the status of extracellular fluid osmolarity, sodium concentration, sense of taste, fluid volume, and BP (Figure 9.1). Signals detected by taste receptors, peripheral osmo-sodium, volume receptors, and arterial/cardiopulmonary baroreceptors reach the nucleus of the solitary tract (NTS) by the VIIth, IXth, and Xth cranial nerves. The other main brain entry of the information related to fluid and cardiovascular balance are the lamina terminalis (LT) and one of the sensory circumventricular organs (CVOs), the area postrema (AP). The LT, consisting of the median preoptic nucleus (MnPO) and the other two sensory CVOs—i.e., subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT) —is recognized as a site in the brain that is crucial for the physiological regulation of hydroelectrolyte balance. The SFO and OVLT lack a blood–brain barrier and contain cells that are sensitive to humoral signals, such as changes in plasma and cerebrospinal fluid sodium concentration (Vivas et al. 1990), osmolality (Sladek and Johnson 1983), and angiotensin II (ANG II) levels (Ferguson and Bains 1997; Simpson et al. 1978). Such unique features make the SFO and OVLT key brain regions for sensing the status of the body fluids and electrolytes. Humoral and neural signals that arrive to the two main brain entries—that is, the CVOs of the LT and within the hindbrain the AP-NTS—activate a central circuit that includes integrative areas such as the MnPO, the paraventricular (PVN), the supraoptic (SON), lateral parabrachial nucleus (LPBN), dorsal raphe nucleus (DRN), and neurochemical systems such as the angiotensinergic, vasopressinergic, oxytocinergic (OT), and serotonergic (5-HT) systems (Figures 9.1 and 9.2). Once these signals act on the above-mentioned neurochemical networks, they trigger appropriate sympathetic, endocrine, and behavioral responses. Therefore, after a body fluid deficit, water and sodium intake and excretion need to be controlled to minimize disturbances of hydromineral homeostasis. In this context, hypovolemia and hyponatremia induced by body fluid depletion stimulate central and peripheral osmo–sodium receptors, taste receptors, volume and arterial/cardiopulmonary baroreceptors, and the renin–angiotensin system (RAS). This latter system, for example, acts mainly through the sensory CVOs and/or the AP to activate brain neural pathways that elevate BP, release vasopressin and aldosterone (ALDO), increase renal sympathetic nerve activity, and increase the ingestion of water and sodium. Among these responses, sodium appetite constitutes an important homeostatic behavior involved in seeking out and acquiring sodium from the environment. Under normal circumstances, the average daily intake of sodium in animals exceeds what is actually needed; however, when they are challenged by environmental (e.g., increased ambient temperature), physiological (e.g., exercise, pregnancy and lactation), or pathophysiological (e.g., emesis, diarrhea, adrenal, or kidney insufficiency) conditions, endocrine and autonomic mechanisms primarily target the kidney, to influence the rate of water and sodium loss, and the vasculature, to maintain arterial BP. Afterward, a behavioral mechanism such as sodium appetite is the means by which sodium loss to the environment is ultimately restored (Geerling and Loewy 2008). It is important to note that in humans, salt appetite is permanently enhanced after perinatal sodium loss (Crystal and Berstein 1995, 1998; Leshem 2009), but putative sodium loss in adults due to, for example, hemorrhage, dehydration, or breastfeeding, does not increase salt appetite significantly; thus, the existence of sodium appetite as a result of sodium loss in adult humans remains controversial (Bertino et al. 1982; Beauchamp et al. 1983, 1987; Leshem 2009).This review will focus on evidence from our laboratory for neurophysiological mechanisms that regulate sodium balance. Specifically, it tries to answer how the brain elicits sodium appetite in response to hyponatremia/hypovolemia associated with sodium depletion, which areas are activated after sodium depletion, how the brain controls the inhibition of this behavior once the deficit is compensated (satiety phase), and what role brain neurochemical groups have for endocrine responses. We close the chapter by analyzing the effects of gonadal hormones and sex chromosome complement (SCC) on sodium appetite and cardiovascular function, respectively.