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Study of mechanisms involved in the remodeling of resistance arteries from ouabain hypertensive rats

Grant number: 12/00217-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Luciana Venturini Rossoni
Grantee:Aldair de França Neto
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hypertension is characterized as a medical condition in which blood pressure is chronically elevated and is of multifactorial origin. Hypertension is frequently associated to functional and/ or structural changes in target organs and metabolic changes. It is known that 50% of patients with essential hypertension have elevated plasma concentrations of endogenous ouabain (OUA). In addition, exogenous administration of this digitalis in animals leads to the development of hypertension. It has been shown that hypertension induced by chronic treatment of rats with the OUA is related to hyper-reactivity in vascular function, increased peripheral vascular resistance and arteriolar remodeling. Over the years our research group has demonstrated the involvement of the renin-angiotensin system (RAS) and endothelin (ET), and the release of vasoconstrictor prostanoids derived from cyclooxygenase (COX), such as thromboxane A2 (TxA2) and PGH2, in genesis and/ or maintenance of hypertension and in the vascular function adjustments observed after chronic treatment with OUA. Thus, it is known that activation of both the RAS as ET is related to the hypertensive response observed in animals treated for five weeks with the OUA, but the ET system as well as the TxA2 / PGH2 seem to be associated with the vascular function adjustments observed in these animals. Moreover, our research group has published that the mesenteric resistance arteries of OUA hypertensive rats have structural and mechanical changes that corroborate the elevation of peripheral vascular resistance and consequently with hypertension in these animals. However, the mechanisms associated with the genesis of arterial remodeling are still unknown. However, systems such as RAS and ET and the association of COX pathway may be possible systems involved in vascular remodeling observed OUA hypertensive animals. Thus, this project aims to study the influence of RAS and ET systems and COX-derived prostanoids in vascular remodeling in mesenteric resistance arteries of animals with hypertension induced by treatment for five weeks with the OUA.

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