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Effect of chronic treatment with everolimus on arterial blood pressure and renal renin angiotensin system in spontaneously hypertensive rats

Grant number: 14/01629-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2014
Effective date (End): November 30, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Dulce Elena Casarini
Grantee:Lys Angela Favaroni Mendes Salgado Ribeiro
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:10/51904-9 - Renin angiotensin and kallikrein kinin systems in hypertension, obesity, diabetes, desnutrition and sepsis: molecular, cellular and physiopathologic mechanisms, AP.TEM

Abstract

High blood pressure (BP) is a multifactorial clinical condition characterized by high and sustained levels of BP. It is frequently associated to functional and/or structural target organs (heart, brain , kidneys and blood vessels) changes with increased risk of cardiovascular events.The hypertension treatment aims/refers not only to reduce BP levels, but also reverse the deleterious effects resulting in target organs. The most commonly used antihypertensive drugs are ACE inhibitors (angiotensin converting enzyme) and AT1 receptor blockers (ARB). The chronic activation of renin angiotensin system (RAS) is one of the main factors that contribute to the hypertension triggering, and also promote an imbalance between ACE and ACE2 proportion, what is related to several cardiovascular and renal diseases.It is known that some of the pathological effect caused by Ang II occurs through mTOR, an intracellular kinase that controls functions such as cell growth and proliferation. Their inhibitors, such as everolimus, has proven to be useful in combating a variety of diseases, including kidney disease progression, including the blood pressure reduction.Based on interaction between mTOR and Ang II, we will study the possible antihypertensive and renoprotective effects of everolimus and RSA inhibitors, alone and in combination, in a chronic way (4 months of treatment) in spontaneously hypertensive rats. Thus, mTOR inhibitors could be interesting candidates for the diseases treatment involving hypertension and kidney damage caused by an imbalance of the renin-angiotensin system.