In vivo investigation of the role played by beta-1 and beta-2 adrenoceptors in the stress-induced alterations in cardiac function

• Grant number: 22/12159-3
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Regina Celia Spadari
• Grantee: Regina Celia Spadari
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Ana Elisa Teófilo Saturi de Carvalho

Abstract

It is now accepted that there is a positive correlation between stress and heart disease. However, the mechanisms underlying this process are still unclear. Several authors have demonstrated in isolated atria, ventricle strips, and papillary muscles that environmental stress may change the sensitivity to catecholamines due to the downregulation of ²1-AR together or not together with altered ²2-AR expression. Additionally, stress may alter the expression and activity of components of the intracellular signaling pathways. So, the hypothesis guiding this project is that environmental stress may reach the molecular level and that such molecular alterations may affect heart performance. The aims of this project are to investigate the role played by ²1 and ²2 adrenoceptors in the putative stress-induced alteration in heart function. Control non-stressed rats and rats submitted to one daily session of foot shock stress (30 min, pulses of 1 mA, 1s, variable intervals of 5-25 s), for 3 days, will be treated with ICI118,551(500 ug/Kg/day, i.p.) or with atenolol (90 mg/Kg/day, i.p.), 2 days before and during the stress period. The heart function will be evaluated 24 h after the last stress session in anesthetized rats, using a catheter inserted in the left ventricle, as follows: heart rate, systolic and diastolic ventricular pressure, mean cardiac pressure, final diastolic pressure, contraction and relaxation rate, the heart response to afterload increase, reaction to preload variation, and heart rate variability (LF, HF and LF/HF). The protein and mRNA of several components of the ²1 and ²2 adrenoceptors signaling pathways will also be evaluated. The results will contribute to a better understanding of the cellular and molecular alterations triggered by stress in the heart, unraveling the mechanisms by which stress may become a risk factor for cardiovascular diseases. (AU)