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Evaluation of cardiovascular and renal effects of selective denervation of renal afferents in 2 kidney, 1 clip wistar rats

Grant number: 17/12383-2
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2017
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Cassia Marta de Toledo Bergamaschi
Grantee:Nathalia Rodrigues Lopes
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

It is known that oxidative stress and increased renal sympathetic nerve activity (rSNA) play an important role in arterial hypertension (AH). Previous studies in our laboratory showed that the angiotensin II (Ang II) - Ang II type 1 receptor (AT-1) -NADPH oxidase axis leads to increased oxidative stress in the kidneys and sympathetic premotor brain regions in an experimental model of renovascular hypertension. Moreover, studies have shown that the renal nerve contributes to the development of renal injury and inflammation and increased renal excretion of proteins. In addition to sympathetic innervation, the kidney is innervated by afferent fibers capable of influencing rSNA. Under physiological conditions, the activation of renal afferent fibers leads to a sympathoinhibitory response and, in contrast, the exacerbated increase in renal afferent nerve activity contributes to the increase in arterial pressure, probably due to a sympathoexcitatory effect in AH. Based on this evidence, the hypothesis of the present project is that renal afferent fibers contribute to AH, sympathoexcitation and renal alterations, such as function, oxidative stress and mechanisms involved in the increase of proteinuria in renovascular hypertensive rats (2-kidney, 1-clip model). Therefore, the present project intends to advance in the elucidation of mechanisms by which renal denervation in hypertensive patients resistant to pharmacological treatment is effective in reducing blood pressure and improving renal function and to contribute to the improvement of new therapeutic strategies for AH. (AU)