Effect of PPAR-alpha and gamma ligands on endothelial dysfunction induced by treatment for 7 days with isoproterenol

• Grant number: 05/00532-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2005
• Effective date (End): July 31, 2007
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Venturini Rossoni
• Grantee: Lívia Emy Fukuda
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases, as heart failure and hypertension, have great epidemiological outstanding in any worldwide health program and are characterized, among other action, by an enhancement of beta-adrenergic receptor stimulation. One experimental model used to mimetize this state is got by daily subcutaneously administration of isoproterenol, a non-selective beta-adrenergic agonist. Studies from our group demonstrated that this treatment can increase the response to vasoconstrictor agents, by an endothelial-dependent pathway on rat aorta. Nowadays, a local inflammatory process was associated with endothelial dysfunction and vascular reactivity alterations in some cardiovascular diseases, like atherosclerosis and hypertension. In particular, chronic beta-adrenergic receptor stimulation can increase the synthesis of pro-inflammatory cytokines in the heart and in the blood vessels of animals submitted to the treatment with isoproterenol, suggesting a relation among inflammation, chronic beta-adrenergic stimulation and vascular dysfuction. A great promising pathway with anti-inflammatory effects and which is able to improve vascular function involves the treatment with ligands of the nuclear receptors “peroxissome proliferator-activated receptors” or PPARs. Thus, the objective of this project will be to evaluate the effects of the PPAR-alpha; and -gamma; ligands on the vascular reactivity and its endothelial modulation of aorta rings from 7 day isoproterenol-treated rats.