Neurochemical circuits involved in fluid and cardiovascular regulation: role of serotonin, oxytocin and angiotensinergic systems

VIVAS L.; GODINO, A.; DALMASSO, C.; CAEIRO X.; MACCHIONE F; CAMBIASSO MJ

?Neurobiology of Body Fluids Homeostasis: Transduction and Integration?

Taylor & Francis Group, LLC

Año: 2011;

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 change 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 a change in arterial blood pressure. The process of sensory integration takes place in different nuclei, with diverse phenotypes and at different levels of the CNS. In order to perform this control, the CNS receives continuous input about the status of extracellular fluid osmolarity, sodium concentration, sense of taste, fluid volume, and blood pressure (see Fig. 1). Signals detected by taste receptors, peripheral osmo/Na, 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 (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 which 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 signals are passed on from the SFO and OVLT to other structures in the central nervous system including the MnPO and the paraventricular (PVN) and supraoptic nucleus (SON), (Lind et al., 1982). Thus, in this regard, the neural regulation of sodium homeostasis can be seen as a neuroendocrine reflex, with two main afferent limbs located in the CVOs of the lamina terminalis and within the hindbrain structures. Moreover, whereas the stimulating hormonal signals are mainly comprised of increased ANG II levels acting on receptive cells located along the lamina terminalis (LT), the inhibitory system involves, in part, central oxytocin (OT) and serotonergic (5HT) pathways (Schematic representation 1). Once the humoral and neural signals act on the abovementioned neural network, 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. This latter system, for example, acts mainly through the sensory CVOs and the NTS to activate brain neural pathways that elevate blood pressure, release vasopressin and aldosterone, increase renal sympathetic nerve activity and increase the ingestion of water and sodium. Among these responses, sodium intake constitutes an important homeostatic behavior involved in seeking out and acquiring sodium from the environment. This motivational state and the related behaviors are referred to as sodium appetite and although, under normal circumstances, the average daily intake of sodium in humans and animals exceeds what is actually needed, 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 blood pressure, but then a behavioral mechanism like sodium appetite is the means by which sodium loss to the environment is ultimately restored. This review will analyze our previous evidence focused on sodium balance regulation after body hyponatremia/hypovolemia induced by sodium depletion that stimulates water and sodium intake. The evidence is reviewed trying to answer how the brain elicits sodium appetite, and particularly, which areas are activated after sodium depletion, how the brain controls the inhibition of this behavior once the deficit is compensated, which brain areas and neuromodulator systems are involved in the satiety phase of sodium appetite, the specific neurochemical groups, their roles, their connections and the associated endocrine responses. We will also analyze how the osmoregulatory mechanisms may be vulnerable to hormonal status during the estrous cycle and estradiol reestablishment after ovariectomy, and finally how renin angiotensin system functioning may be under the control of sex chromosome complement regardless of the gonadal status of the animals.