Study of the Effects of Aerobic Physical Training on Hemodynamic, Morphological, and Functional Cardiac Adaptations in Hypertensive Female Rats Undergoing Ovarian Hormone Deprivation.

• Grant number: 24/16796-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Hugo Celso Dutra de Souza
• Grantee: Leticia Araujo Ruys
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Molecular and cellular damage throughout life can lead to the development of pathological conditions. However, premenopausal women exhibit a lower incidence of cardiovascular diseases (CVDs) when compared to men of the same age. This lower predisposition to developing cardiovascular disorders is often attributed to the influence of ovarian hormones, particularly estrogens. After menopause, hormonal changes can cause adverse effects on cardiometabolic health, including damage to vascular and cardiac tissue. In cardiac tissue, these damages involve an increase in collagen deposition in the extracelular matrix, leading to a higher percentage of fibrous tissue and reduced cardiac functionality, mainly in individuals who have cardiometabolic disorders, such as systemic arterial hypertension. The mechanisms involved in these adaptations remain uncertain, but recente studies conducted in our laboratory provide evidence suggesting the involvement of intracelular and extracellular matrix proteases, such as calpain-1 (CAPN1) and metalloproteinase-2 (MMP2). Based on the adverse effects of ovarian hormone deprivation, there is an urgent need for both pharmacological and non-pharmacological therapies to mitigate these damages. In this context, aerobic physical training is a non-pharmacological tool that has shown effective in reducing fibrous tissue percentage, as well as in addressing the morphological and functional cardiac damage secondary to ovarian hormone deprivation. However, the mechanisms involved in these adaptations remain uncertain. We hypothesize that CPN-1 and MMP-2 might play a role in this process. OBJECTIVES: Evaluation of the modulatory role of aerobic physical training in cardiac fibrosis secondary to ovarian hormone deprivation, as well as in CPN-1 and MMP-2 expression and activity in Wistar Kyoto and SHR (Spontaneously Hypertensive Rats). Additionally, as secondary objectives, we address assessing the cardiac morphofunctionality by echocardiography, left ventricular contractility and coronary bed reactivity in isolated hearts, and evolution of blood pressure and heart rate using tail plethysmography. METHODS: 64female rats were divided equally into two groups: normotensive (Wistar-Kyoto) and hypertensive (SHR). Each group will be further subdivided into two subgroups: rats undergoing ovariectomy (OVX) surgery at 18 weeks of age and rats undergoing sham surgery (SHAM) at 18 weeks of age. Following a two-week recovery period from the surgical procedure, the aerobic physical training protocol will be initiated. This protocol will consist of 14 weeks of swimming in a glass tank, with a daily duration of 45 minutes for five times per week. Blood pressure and heart rate changes will be recorded using tail plethysmography. Left ventricular morphofunctional analysis will be performed using bidimensional echocardiography. Leftventricular contractility and coronary bed reactivity will be evaluated using the Langendorff technique in isolated hearts. The expression and activity of calpain-1 and MMP-2 will be analyzed using Western blot and immunofluorescence techniques, respectively.