Efeitos da administração do Alisquireno em rins de ratos com hipertensão renovascular

Abstract

Systemic arterial hypertension is a multifactorial clinical condition characterized by persistent elevated blood pressure levels, which is one of the main causes of death in the world. Hypertension may be primary or secondary. Renovascular hypertension represents one of the most common causes of secondary hypertension and its progress is associated with ischemia of the kidney, leads to the overactivation of the renin angiotensin aldosterone system (RAAS), culminating in an increase of renin release and, consequently, angiotensin II levels, which causes systemic changes such as increased blood volume, vasoconstriction, activation of the sympathetic nervous system and retention of sodium and water, resulting in elevated blood pressure. In addition to systemic alterations, local changes occur, such as oxidative stress, macrophage infiltration, release of proinflammatory cytokines, dysfunction and tissue fibrosis in the kidney. Blockage of RAAS reduces blood pressure and reduces the progression of kidney disease. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the present work had as objective to analyze the morphophysiology of the left kidney of male Wistar rats with renovascular hypertension after the treatment with Aliskiren. In order to induce hypertension, the animals were submitted to surgical procedure according to the experimental model 2 Kidney-1 Clip of Goldblatt, causing stenotic left renal artery. The following parameters were analyzed: systolic blood pressure, plasma and urinary levels of creatinine, urea, phosphorus, albumin and proteins, renal cortex structure and ultrastructure, fibrosis and tissue inflammation and metalloproteinase activity. Thus, our results showed that the hypertensive animals treated with Aliskiren presented lower blood pressure and reestablishment of renal function with lower levels of plasma creatinine and urinary proteins. In addition, remodeling of the morphological alterations imposed by renovascular hypertension through the reduction of fibrosis and expression of renin, laminin and pro-inflammatory cytokines, such as TNF-α, TGF-β and IL-6, as well as restoration of integrity of the glomerular filtration barrier. Therefore, our findings suggest that the treatment with Aliskiren has renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertension.