Signal Transduction of Mineralocorticoid and Angiotensin II Receptors in the Central Control of Sodium Appetite: A Narrative Review.

Sodium appetite is an innate behavior occurring in response to sodium depletion that induces homeostatic responses such as the secretion of the mineralocorticoid hormone aldosterone from the zona glomerulosa of the adrenal cortex and the stimulation of the peptide hormone angiotensin II (ANG II). The synergistic action of these hormones signals to the brain the sodium appetite that represents the increased palatability for salt intake. This narrative review summarizes the main data dealing with the role of mineralocorticoid and ANG II receptors in the central control of sodium appetite. Appropriate keywords and MeSH terms were identified and searched in PubMed. References to original articles and reviews were examined, selected, and discussed. Several brain areas control sodium appetite, including the nucleus of the solitary tract, which contains aldosterone-sensitive HSD2 neurons, and the organum vasculosum lamina terminalis (OVLT) that contains ANG II-sensitive neurons. Furthermore, sodium appetite is under the control of signaling proteins such as mitogen-activated protein kinase (MAPK) and inositol 1,4,5-thriphosphate (IP3). ANG II stimulates salt intake via MAPK, while combined ANG II and aldosterone action induce sodium intake via the IP3 signaling pathway. Finally, aldosterone and ANG II stimulate OVLT neurons and suppress oxytocin secretion inhibiting the neuronal activity of the paraventricular nucleus, thus disinhibiting the OVLT activity to aldosterone and ANG II stimulation.

Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure.

INTRODUCTION: Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and Methods of Search: To overview the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English. RESULTS: Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. ANG II stimulates VP release via angiotensin receptor 1. ANG II and VP stimulate aldosterone synthesis and secretion and enhance its action at the renal collecting duct level. VP is also involved in the cardiovascular reflex control of the sympathetic nervous system (SNS). Also, VP potentiates vasoconstriction and cardiac contractility, enhancing the effect of ANG II on sympathetic tone and arterial pressure. On the other hand, ANG II and VP act antagonistically in regulating baroreflex control of the SNS. There is evidence that high VP plasma levels increase baroreflex sympatho-inhibitory responses, and the arterial baroreflex response is shifted to lower pressure. This cardiovascular reflex control is mediated mainly in the brain, specifically in the circumventricular organ area postrema (AP). The modulation of cardiovascular reflex control induced by VP is abolished after lesions of the AP. VP modulation of baroreflex function is also under the control of α2-adrenergic pathway arising from the nucleus of the solitary tract (NTS) and synapsing on VP-ergic neurons of supraoptic and paraventricular nuclei. Presynaptic α2-adrenergic stimulation within the NTS inhibits VP release induced by hypovolemia and the effects of VP and AP on baroreflex control of SNS, thus showing baroreceptor afferent inputs are processed within the NTS and contribute to the increased baroreflex sympatho-inhibitory responses. DISCUSSION: In patients with congestive heart failure (CHF), plasma VP levels are elevated, inducing an up-regulation of aquaporin 2 water channel expression in renal collecting duct (CD) cells provoking exaggerated water retention and dilutional hyponatremia. Antagonists of VP and ANG II receptors reduce edema, body weight, and dyspnea in CHF patients. CONCLUSION: Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses.

OBJECTIVE: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We perform a review of the literature, aiming at providing the current concepts regarding the angiotensin interaction with the immune system in the brain and the related implications for cardiovascular and neuroendocrine responses. METHODS: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. RESULTS: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release, sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema, paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the development of hypertension. CONCLUSION: Besides the well-known mechanisms by which RAAS activation can lead to the development of hypertension, the interactions between ANG II and the immune system at the brain level can play a significant role.