Role of the proximal tubule Na+/H+ exchanger isoform 3 in the acute sodium and water retention after 24 hours of water deprivation: aresponse to arginine vasopressin ou to the renin-angiotensin-aldosterone system?

• Grant number: 13/11848-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2014
• End date: March 31, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Gerhard Malnic
• Grantee: Thaissa Dantas Pessoa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The renal system is important to the osmolarity balance of the extravascular fluid and one of the most important systems related to the control of the extracellular fluid volume and the arterial pressure.The renal control of osmolarity is achieved through a complex mechanism able to secrete water or retain it depending on the needs of the body. This function is performed by arginine-vasopressin (AVP) (also known as antidiuretic hormone, HAD), which acts specially at the distal segments of the nephron according to the currently knowledge. AVP is a peptidic hormone secreted by hypophysis during increases in the plasmatic osmolarity. Besides that, it is also secreted during severe decrease of extracellular volume or arterial pressure.Although kidneys are able to perform water retention dissociated to solute retention, in several conditions the increase in the osmolarity occurs in parallel to volume decrease - as seen in conditions of hypovolemic dehydration. Thus, during water deprivation, the renal mechanisms of sodium balance as well the mechanism of osmolarity control are activated in parallel and may produce functional overlap. Currently, NHE3 is known as an important protein related to volume maintenance, which was associated only to distal nephron proteins before. Nevertheless, there isn't any study regarding the effect of water deprivation on the activity of this transporter, even after the discovery of a receptor to AVP in the proximal tubule. Besides that, there is an uncertainty related about the role of NHE3 in sodium and volume retention during water deprivation and which hormones could be involved: if only the RAAS is able to modulate NHE3, through AGII or if AVP is also able to modulate the exchanger.The study of the effects of water deprivation in the renal function is essential to the implementation of rehydration therapies in countries which part of the population suffers from water shortage, like in the northeast of Brasil. The goal of the present project is determine the role of NHE3 in the proximal tubule in the sodium and water retention after water deprivation. We also pretend to determine if AVP is able to modulate NHE3 activity and the role of this hormone in the NHE3-dependent sodium and water retention after water deprivation. Besides that, we aim to define if the RAAS is also involved in NHE3 modulation in this condition.