Papel dos aferentes renais sobre atividade vasomotora simpática durante administração aguda de furosemida na hipertensão renovascular
Data
2022-05-31
Autores
Carvalhal, Rafael Santos 
Orientadores
Campos Junior, Ruy Ribeiro
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A comunicação entre os rins e o sistema nervoso central (SNC), sobretudo, a sinalização hormonal e simpática tem sido amplamente estudadas. Entretanto, pouco se sabe sobre o papel dos aferentes renais no controle cardiovascular e renal em condições normais e fisiopatológicas. O presente estudo teve como objetivo analisar o papel dos aferentes renais no controle vasomotor simpático, para o qual foi utilizado o modelo de hipertensão renovascular Goldblatt 2 rins, 1 clipe (2R1C). A furosemida em doses subdiuréticas administrada sistemicamente leva a simpatoexcitação mediada por aferente renal em ratos normotensos. Portanto, aventamos a hipótese de que a infusão intravenosa aguda de furosemida pode ativar aferentes renais que regulam a atividade nervosa vasomotora simpática no modelo 2R1C. Para testar essa hipótese, realizamos o registro simultâneo dos nervos renais e esplâncnicos em ratos 2R1C e respectivos controles durante a infusão de furosemida. Além disso, foi investigado o papel dos aferentes renais nas respostas vasomotoras simpáticas desencadeadas pela furosemida em ratos submetidos à deaferentação renal seletiva por capsaicina. O presente estudo revelou que a Furosemida produziu: 1) Maior redução da PAM em ratos CTR-Dax do que em CTR (CTR vs CTR-DAX: 100min, 6 ± 5* vs -19 ± 5 mmHg*; 120min, -9±6* vs -23±3 mmHg*); 2) Maior redução de PAM no grupo 2R1C do que no grupo CTR (CTR vs 2R1C: -6±2 vs -18±7 mmHg*); 3) Redução de ANSr-UA no grupo 2R1C porém não no grupo controle (100min: -0,16 ± 0,07248); 4) Aumento da ANSr-UA nos animais 2R1C-Dax quando comparados aos 2R1C (2R1C-dax vs 2R1C: 30min, 0,06 ± 0,05 AU vs -0,10 ± 0,06 AU). Portanto, durante a infusão de furosemida (dose subdiurética), os aferentes renais se mostraram importantes mediadores para a ativação simpática renal em animais controles, além disso, esses aferentes se comportaram de forma diferente nos animais 2R1C e CTR, após a furosemida. Por fim, os aferentes renais, ativados por furosemida, causam simpatoinibição em animais hipertensos, mas não no grupo controle, constatado pela deaferentação de animais 2R1C. A hiperatividade simpática renal em ratos Goldblatt é, em parte, dependente de aferentes renais.
Communication between the kidneys and the central nervous system (CNS), especially hormonal and sympathetic communications, are the most studied. However, little is known about the role of renal afferents in cardiovascular and renal control under normal and pathophysiological conditions. The present study aimed to analyze the role of renal afferents in sympathetic vasomotor control, for which the Goldblatt 2 kidney, 1 clip (2K1C) renovascular hypertension model was used. Furosemide systemically administered (sub diuretic dose) leads to renal afferent-mediated sympathoexcitation in normotensive rats. Therefore, we hypothesize that acute intravenous infusion of furosemide may activate renal afferents that regulate sympathetic vasomotor nerve activity. To test this hypothesis, we perform the simultaneous registration of renal and splanchnic nerves in 2K1C rats and respective controls during furosemide infusion. In addition, the role of renal afferents in the sympathetic vasomotor responses triggered by furosemide in rats submitted to selective renal deafferentation by capsaisin was investigated. The main findings of this study were that Furosemide produced: 1) Greater MAP reduction in CTR-Dax than in CTR rats (CTR vs CTR-DAX: 100min, 6 ± 5* vs -19 ± 5 mmHg*; 120min, - 9±6* vs -23±3 mmHg*); 2) Greater MAP reduction in the 2K1C group than in the CTR group (CTR vs 2K1C: -6±2 vs -18±7 mmHg*); 3) Reduction of rSNA-UA in the 2K1C group but not in the control group (100min: -0.16 ± 0.07248); 4) Increase in rSNA-UA in 2K1C-Dax animals when compared to 2K1C (2K1C-dax vs 2K1C: 30min, 0.06 ± 0.05 AU vs -0.10 ± 0.06 AU). Therefore, during furosemide infusion (subdiuretic dose), renal afferents appear to be important mediators for renal sympathetic activation in control animals, in addition, these afferents behaved differently in 2K1C and CTR animals after furosemide. Finally, renal afferents, activated by furosemide, cause sympathoinhibition in hypertensive animals, but not in the control group, as evidenced by the deafferentation of 2K1C animals. Thus, renal sympathetic hyperactivity in Goldblatt rats is in part dependent on renal afferents.
Communication between the kidneys and the central nervous system (CNS), especially hormonal and sympathetic communications, are the most studied. However, little is known about the role of renal afferents in cardiovascular and renal control under normal and pathophysiological conditions. The present study aimed to analyze the role of renal afferents in sympathetic vasomotor control, for which the Goldblatt 2 kidney, 1 clip (2K1C) renovascular hypertension model was used. Furosemide systemically administered (sub diuretic dose) leads to renal afferent-mediated sympathoexcitation in normotensive rats. Therefore, we hypothesize that acute intravenous infusion of furosemide may activate renal afferents that regulate sympathetic vasomotor nerve activity. To test this hypothesis, we perform the simultaneous registration of renal and splanchnic nerves in 2K1C rats and respective controls during furosemide infusion. In addition, the role of renal afferents in the sympathetic vasomotor responses triggered by furosemide in rats submitted to selective renal deafferentation by capsaisin was investigated. The main findings of this study were that Furosemide produced: 1) Greater MAP reduction in CTR-Dax than in CTR rats (CTR vs CTR-DAX: 100min, 6 ± 5* vs -19 ± 5 mmHg*; 120min, - 9±6* vs -23±3 mmHg*); 2) Greater MAP reduction in the 2K1C group than in the CTR group (CTR vs 2K1C: -6±2 vs -18±7 mmHg*); 3) Reduction of rSNA-UA in the 2K1C group but not in the control group (100min: -0.16 ± 0.07248); 4) Increase in rSNA-UA in 2K1C-Dax animals when compared to 2K1C (2K1C-dax vs 2K1C: 30min, 0.06 ± 0.05 AU vs -0.10 ± 0.06 AU). Therefore, during furosemide infusion (subdiuretic dose), renal afferents appear to be important mediators for renal sympathetic activation in control animals, in addition, these afferents behaved differently in 2K1C and CTR animals after furosemide. Finally, renal afferents, activated by furosemide, cause sympathoinhibition in hypertensive animals, but not in the control group, as evidenced by the deafferentation of 2K1C animals. Thus, renal sympathetic hyperactivity in Goldblatt rats is in part dependent on renal afferents.