Efeitos do tratamento combinado com alisquireno e L-arginina sobre a reatividade vascular em anéis de aorta de ratos com hipertensão renovascular

• Autor(a) principal: Santuzzi, Cintia Helena
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/8068
• topic: 2K1C hypertension; endothelial dysfunction; aliskiren; L-arginine; oxidative stress; RAAS; hipertensão renovascular; disfunção endotelial; alisquireno; Larginina; sistema renina-angiotensina; stress oxigênio; Fisiologia; 612

Angiotensin II is a key player in pathogenesis of renovascular hypertension and this condition is associated with endothelial dysfunction. We investigate aliskiren, Larginine and association of treatments on blood pressure (BP) and vascular reactivity in aortic rings. Hypertension was induced in male Wistar rats by clipping the left renal artery and animals were divided: Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+aliskiren (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+aliskiren and L-arginine (ALSK+L-arg) treatment for 4 weeks. Blood pressure was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg decreased blood pressure, contractile response to phenylephrine and improved the acetylcholine relaxation. Endothelium removal and incubation with L-NAME increased the response to phenylephrine in all groups, but magnitude was higher in ALSK+L-arg group. Enalapril reduced phenylephrine response in 2K1C and ALSK groups and Losartan reduced contractile response in all of the groups. Apocynin reduced contractile response in 2K1C, ALSK and ALSK+L-arg groups and incubation with superoxide dismutase (SOD) reduced phenylephrine response in 2K1C and ALSK groups. eNOS expression increase in 2K1C and L-arg groups and iNOS increased only in 2K1C group compared with other groups. AT1 expression increase in 2K1C compared to Sham, ALSK and ALSK+L-arg groups, AT2 expression increase in ALSK+L-arg group compared to Sham and L-arg groups, Ms SOD2 increased in ALSK+L-arg group compared to 2R1C, ALSK and Larg group, on the other hand, gp91phox decreased in ALSK+L-arg compared with 2K1C and ALSK. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats and the mechanisms responsible appear to be related to the modulation of local reninangiotensin system, which is associated with the reduction in endothelial oxidative stress.