Evaluation of aortic perivascular adipose tissue function in pre-hypertensive spontaneously hypertensive rats: effect of mitochondrial antioxidant treatment with MitoTEMPO

• Grant number: 23/09161-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date until: October 01, 2023
• End date until: December 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Venturini Rossoni
• Grantee: Beatriz Monteiro Curcio
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/01153-0 - Evaluation of the interaction between eNOS uncoupling and mitochondrial oxidative stress in adipocytes, BE.EP.IC

Abstract

After 1991, with the discoveries of the essential role of the perivascular adipose tissue (PVAT) in the regulation of vascular tone, it has become an important target of studies that aim to understand its functioning under physiological and pathological conditions. Known for its anticontractile effect, PVAT modulates the degree of contraction of vascular smooth muscle cells through the release of vasoactive substances, both vasodilators and/or vasoconstrictors, while under physiological conditions the release of vasodilator factors are more pronounced. However, in cardiometabolic diseases, such as hypertension, it has been shown that the PVAT is dysfunctional. Characterized by a chronic increase in blood pressure, hypertension is a public health problem, being one of the main chronic diseases worldwide. It is well known that essential hypertension has a strong genetic component linked to its development, with a gradual evolution over the years, resulting from structural and functional cardiovascular adjustments. It has already been demonstrated, in an animal model of essential hypertension - SHR (spontaneously hypertensive rats) - the presence of vascular remodeling, but not endothelial dysfunction, in the pre-hypertensive stage. However, these functional studies were performed in vascular rings without PVAT. So far, little is known about the role of PVAT in this model, especially in the stage that precedes the development of hypertension. Dysfunction of the thoracic aorta PVAT of SHR has already been associated with the reduction of vasodilator mediators, whitening, and local inflammation. Previous results from our research group associate the observed dysfunction with lower response induced by nitric oxide, eNOS uncoupling, and the presence of oxidative stress, with impairment of the mitochondrial antioxidant defense. Therefore, this project aims to evaluate the function of thoracic aorta PVAT in pre-hypertensive SHR and the effect of early treatment with the mitochondrial antioxidant MitoTEMPO.