DISERTANTE SIMPOSIO ?TRPV1 osmosensitive channel involvement in the control of sodium appetite?

A. GODINO; C. PORCARI; DEBARBA LK; CAEIRO X.; REIS L; ANTUNES-RODRIGUES J; VIVAS L.

Simposio; 22nd International Symposium on Regulatory Peptides; 2018

International Regulatory Peptide Society (IRPS)

SELECCIONADO COMO COMUNICACION ORALGodino A.1,5, Porcari CY1, Debarba LK 3, Caeiro XE1, Reis L2, Mecawi A2, Antunes-Rodrigues J3, Vivas L1,41.Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina;2.Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro, Seropedica, Brazil;3.Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil4.Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina5.Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, ArgentinaChanges in body water/sodium balance are tightly controlled by central and peripheral osmo?sodium receptors among others, which trigger the activity of a central network that mainly release vasopressin and/or aldosterone, increase renal sympathetic nerve activity, and induce thirst and sodium appetite. The main central osmoreceptive neurons are in the circumventricular organs of the lamina terminalis, i.e. the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and along the hypothalamic magnocellular cells. It has been postulated that their intrinsic osmosensitivity is mediated in part by different types of channels, TRPV1, TRPV4, NaX and EnaC. The function of TRPV1 channel has been previously analyzed using knockout (KO) TRPV1 mice; however its functional role after different types of hyperosmotic thirst remains controversial (Ciura and Bourque 2006; Kinsman et al., 2014). On the other hand the TRPV1 channel involvement in the control of sodium appetite (SA) induced by sodium depletion (SD) has not been yet analyzed. The aim of the present work was to explore the TRPV1 channel involvement in the genesis of the SA that prompts a new role for TRPV1 channel. We used the TRPV1 KO mice model to analyze basal and induced SA by SD. In this model we studied the renal responses and the TRPV4, NaX and angiotensin type 1 receptor (AT1a) RNAm expression within the SFO and OVLT. We also recorded sodium and water intake and the renal excretion at 2 h and 24 h after SD induced by furosemide (50mg/kg) in combination with low sodium diet in wild type (WT) and KO mice. After SD, the KO animals showed an increase in the sodium preference (F=8.49; p=0.006) and consumed a higher hypertonic cocktail (F=8.49; p=0.0059) in relation to WT animals, independent of the time after SD. These data suggest that KO animals, when stimulated to drink water and sodium, make a hypertonic cocktail instead of the isotonic one usually made by the control animals. The urinary volume (F=5.45; p=0.0003) and sodium excretion (F=3.99; p=0.028) induced by Furosemide at 30 minutes were both reduced in KO animals in comparison to WT. There was no change in plasma osmolality between the groups 2 h and 24 h after SD. Interestingly, 2 hs after SD, the WT animals, showed an increased expression of TPRV4 channels along the SFO and in comparison to KO mice (F = 5.11, p < 0.05). In sum, these data suggest that TPRV1 KO animals have a differential renal and behavioral response after sodium depletion. Besides, in contrast to WT animals, they did not show any changes in the SFO TRPV4 expression early after sodium depletion. In conclusion our results suggest that the TRPV1 channels are involved in the osmoregulatory processes after an acute body sodium depletion possibly to modulate renal and intake responsesSupport: CNPq; CONICET; FONCYT, SECYT.