Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-01-24T15:47:47Z No. of bitstreams: 1 2016 - L?via da Rocha Natalino Monteiro.pdf: 1451629 bytes, checksum: c984d90970fa9192a11dedd19eb857df (MD5) / Made available in DSpace on 2017-01-24T15:47:47Z (GMT). No. of bitstreams: 1 2016 - L?via da Rocha Natalino Monteiro.pdf: 1451629 bytes, checksum: c984d90970fa9192a11dedd19eb857df (MD5) Previous issue date: 2016-02-17 / Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do RJ - FAPERJ / The constant regulation of sodium and water balance is essential for the maintenance of life. From the simplest to the most complex organisms, conservation of such elements at appropriate levels is a vital issue for the homeostasis of the individual. In order to maintain this balance, organisms resort a set of neurohumoral mechanisms that constantly regulate the content of bodily water and sodium. In recent decades, studies of neural mechanisms involved in the regulation of sodium appetite have gained ground since the excessive intake of sodium chloride has been directly related to functional changes which can lead to diseases such as hypertension. Besides the high daily consumption of sodium chloride by occidental societies, there is also a growing number cases of hypertension, particularly the so-called ?salt-sensitive?. Therefore, it is necessary that the mechanisms involved in these changes are intensively studied in scientific models. Thus, through the use of an animal model, we investigated the functional changes arising from the modification of sodium content in the diet of animals. Wistar male rats were randomly divided into 4 groups: i) control (CTRL); ii) low-sodium diet (LSD); iii) furosemide (FURO); iv) saline overload (SO). From this division, we draw the hydroelectrolytic, cardiovascular and molecular profiles of these paradigms four days after the protocols beginning. We found that low-sodium diet and furosemide were able to induce a sustained sodium appetite 4 hours after reintroduction of fluids when compared to control group (LSD: 4.1 ? 0.8 and FURO: 8.5 ? 1.0 vs. CTRL 0.15 ? 0.08 mL/100g body weight, p<0.05, respectively). Besides we have confirmed the occurrence of hypernatremia in SO group (163.7 ? 1.6 vs. 143.2 ? 0.7 mEq/L, p<0.05) we surprisingly have found higher plasma sodium levels in LSD (148.7 ? 1.0 vs. 143.2 ? 0.7 mEq/L, p<0.05) when compared to control group. During the assessment of cardiac parameters, only the FURO group showed smaller mean arterial pressure than control after administration of phenylephrine at both 10 and 50 ?g/mL concentrations (Phe10: 142.6 ? 19.1 vs. 222.4 ? 14 bpm, p<0.05; Phe50: 261.0 ? 74.8 vs. 190.9 ? 19.6 mmHg, p<0.05, respectively), probably due to hypovolemia, a factor which could also explain the absence of hyponatremia in these animals. Concerning the molecular parameters within the PVN, SO group showed an increased mRNA expression of AVP (2.61 ? 0.16 vs. 1.04 ? 0.04 a.u., p<0.05) and OT (1.52 ? 0.12 vs. 1.01 ? 0.05 a.u., p<0.05), while in the LSD group, these parameters are reduced (AVP: 0.65 ? 0.07 vs. 1.04 ? 0.04 a.u., p<0.05; OT: 0.65 ? 0.06 vs. 1.01 ? 0.05 a.u., p<0.05), when compared to control group, respectively. Finally, we found increased levels of AT1 receptor mRNA in SO group (2.94 ? 0.26 vs. 1.14 ? 0.25 a.u, p<0.05) and FURO (3.08 ? 0.51 vs. 1.14 ? 0.25 a.u, p<0.05) compared to control, respectively. Thus, these results underscore the central role of neuroendocrine systems in the modulation of electrolyte and cardiovascular homeostasis / A regula??o constante do balan?o de ?gua e s?dio ? essencial para a manuten??o da vida. Desde os organismos mais simples at? os mais complexos, a conserva??o de tais elementos em n?veis adequados constitui ponto crucial para a homeostase do indiv?duo. Para tanto, os organismos lan?am m?o de uma s?rie de mecanismos neuro-humorais que regulam a todo momento o conte?do de ?gua e s?dio corporal. Nas ?ltimas d?cadas, estudos sobre mecanismos neurais envolvidos na regula??o do apetite ao s?dio t?m ganhado destaque, uma vez que o consumo exagerado de cloreto de s?dio est? diretamente relacionado a altera??es funcionais que podem gerar doen?as como a hipertens?o arterial. Al?m do alto consumo di?rio de s?dio pelas sociedades ocidentais, h? tamb?m um crescente n?mero de casos de hipertens?o arterial, particularmente do tipo denominado sal-sens?vel. Assim, ? necess?rio que os mecanismos envolvidos nessas altera??es sejam intensamente estudados em modelos cient?ficos. Desta forma, atrav?s do uso de modelo animal, investigamos neste trabalho as altera??es funcionais advindas da modifica??o do conte?do de s?dio presente na dieta dos animais. Para tanto, ratos Wistar machos foram randomicamente divididos em 4 grupos experimentais: i) controle (CTRL); ii) dieta pobre em s?dio (DP); iii) furosemida (FURO); iv) sobrecarga salina (SS). A partir desta divis?o, tra?amos os perfis hidroeletrol?tico, cardiovascular e molecular desses paradigmas de desafio ao balan?o hidroeletrol?tico. Verificamos que a dieta hiposs?dica e a furosemida foram capazes de induzir o apetite ao s?dio de forma sustentada at? 4 horas ap?s reapresenta??o de fluidos (DP 4,1 ? 0,8 de peso corporal; FURO 8,5 ? 1,0 vs. CTRL 0,15 ? 0,08 mL/100g; p<0,05). Confirmamos a ocorr?ncia de hipernatremia a partir da sobrecarga salina (SS 163,7 ? 1,6 vs. CTRL 143,2 ? 0,7 mEq/L; p<0,05) e, surpreendentemente, encontramos n?veis natr?micos maiores que o controle no grupo DP (DP 148,7 ? 1,8 vs. Ctrl 143,2 ? 0,7 mEq/L; p<0,05). Quanto ? avalia??o dos par?metros card?acos, somente o grupo furosemida apresentou PAM menor que o controle ap?s a administra??o de fenilefrina nas concentra??es de 10 e 50 ?g/mL ( Phe10 = Furo 142,6 ? 19,1 vs. Ctrl 222,4 ? 14,2 ; Phe50 = Furo 261,0 ? 74,8 vs. Ctrl 190,9 ? 19,6 mmHg; p<0,05), provavelmente devido ? hipovolemia nestes animais. Verificamos ainda que no grupo submetido ? sobrecarga salina ocorre aumento da express?o de mRNA para AVP (SS 2,61 ? 0,16 vs. CTRL 1,04 ? 0,04 a.u - unidades arbitr?rias; p<0,05) e OT (SS 1,52 ? 0,12 vs. CTRL 1,01 ? 0,05 a.u; p<0,05), enquanto que no grupo dieta pobre estes par?metros s?o reduzidos (AVP - DP 0,65 ? 0,07vs. CTRL 1,04 ? 0,04; OT - DP 0,65 ? 0,06vs. CTRL 1,01 ? 0,05 a.u; p<0,05). Por fim, encontramos n?veis aumentados de mRNA do receptor AT1 nos grupos sobrecarga salina (SS 2,94 ? 0,26 vs. CTRL 1,14 ? 0,25 a.u; p<0,05) e furosemida (Furo 3,08 ? 0,51 vs. CTRL 1,14 ? 0,25 a.u; p<0,05). Deste modo, estes resultados refor?am o importante papel dos sistemas neuroend?crinos centrais na modula??o da homeostase hidroeletrol?tica e cardiovascular