The importance of angiotensin II in the vascular inflammatory process

• Grant number: 09/15693-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2010
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Silvia Lacchini
• Grantee: Silvia Lacchini
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The hypothesis of the present project is that the angiotensin II (AngII), when it is acting on his receptors AT1 and AT2, is able to start initial inflammatory process, which can compose part of the mechanisms wrapped in the process of vascular injury or even increase the predisposition to develop the injury. To test this hypothesis, the objectives of the present project are: 1) to value the expression of initial markers of inflammation in response to the action of the AngII, and 2) to value for which receptor (AT1 or AT2) the AngII leads to the expression of these inflammatory markers. The study will be done in male mice C57Bl/6J, submitted to subpressor doses of angiotensin II, AngII receptor blockers and a combination of these. The times of AngII treatment will be determined in a curve of time-response to subpressor injections of angII. Six groups will be prepared: control and treated with ang II, losartan, ang II plus losartan, PD123.319 and ang II plus PD123.319. After the time of treatment, the animals will be sacrificed and will proceed the collection of arteries (aorta and carotid), heart, kidneys and lung for analysis of inflammatory mediators. Evaluations will be done to evaluate possible tissue edema. The evaluation of the inflammatory markers will be done for immunoistochemistry, studying the cytokines IL-1beta and IL-6, TNF-alpha, TGF-beta and MCP-1, the adhesion molecules VCAM-1 and ICAM-1, and a marker of inflammatory cells (CD 45). Moreover, there will be studied inflammatory markers (IL-1beta, IL-6 and TNF-alpha) by ELISA. After that, will be studied the possible intracellular pathways that determine angiotensina II influence in studied arteries. (AU)