Effect of chronic ethanol consumption on the anti-contractile phenotype displayed by rat aorta perivascular adipose tissue

• Grant number: 16/20498-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2017
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Renato Tirapelli
• Grantee: Sthefany Teodoro Ricci
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chronic ethanol intake induces significant changes in vascular function, and for this reason it is considered an important risk factor in the development of cardiovascular diseases, such as hypertension. Vascular dysfunction induced by chronic ethanol consumption involves the generation of reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO) in the vasculature. Ethanol consumption increases the activity of NAD(P)H oxidase, which is the main source of superoxide anions (O2-) in the vasculature. The cellular levels of O2- are regulated by the enzyme superoxide dismutase (SOD), which converts O2- into hydrogen peroxide (H2O2). The latter is more stable than O2- and is related to vascular dysfunction. Currently, it is known that the perivascular adipose tissue (PVAT) releases vasoactive substances that participate in the regulation of the vascular tone. PVAT displays anti-contractile action and express components of the renin-angiotensin system, NAD(P)H oxidase, the endothelial nitric oxide synthase (eNOS), and all isoforms of SOD. Together, these elements participate in the regulation and maintenance of the vascular tone. However, in non-physiological conditions modifications on PVAT phenotype may occur. These include the loss of its anti-contractile effect. For example, in hypertension, obesity and diabetes mellitus PVAT induces vascular dysfunction mainly by the following mechanisms: 1) increased oxidative stress; 2) reduction in eNOS expression and synthesis. However, the effect of chronic ethanol consumption on the anti-contractile phenotype of PVAT has not been evaluated. The hypothesis of this study is that chronic ethanol consumption will induce functional alteration of the PVAT with increased production of ROS via NAD(P)H oxidase and reduced bioavailability of NO. Together, these responses would lead to the loss of the anti-contractile phenotype of PVAT. Thus, this project was designed to investigate the effect of chronic ethanol consumption on the anti-contractile action of PVAT in the rat aorta and the involvement of ROS and the NO pathway in such response. (AU)