EFFECTS OF OVARIAN HORMONE DEPRIVATION ON CARDIAC FIBROSIS AND ¿-ADRENERGIC RECEPTOR EXPRESSION IN SPONTANEOUSLY HYPERTENSIVE RATS

• Grant number: 25/14799-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Hugo Celso Dutra de Souza
• Grantee: Giulia Vitória Andrade
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Introduction: Systemic arterial hypertension (SAH) is associated with various functional and structural alterations in the heart, including reduced cardiac contractile capacity, changes in coronary bed reactivity, and increased cardiac fibrosis. However, in women of reproductive age, this condition may be less severe due to the cardiovascular protection provided by ovarian hormones. In this context, physiological ovarian failure (menopause) represents a critical turning point in this protection, potentially promoting more severe changes in cardiac contractility and coronary bed reactivity. In this scenario, a previous study conducted in our laboratory evaluated the effects of late ovarian hormone deprivation (a simulation of menopause) on the cardiac contractility of normotensive and spontaneously hypertensive rats. The results indicated significant effects of both SAH and ovariectomy on coronary perfusion pressure, with higher values observed in hypertensive and ovariectomized rats. A significant effect of SAH was also found on dP/dT minimum, with more negative values in the hypertensive groups. These findings suggest increased vascular resistance, possibly related to greater fibrotic tissue deposition, and the activation of compensatory mechanisms to preserve cardiac function under the increased afterload imposed by SAH. Among these mechanisms, modulation of ¿-adrenergic receptor expression stands out, as these receptors are essential for regulating myocardial contractility. However, the literature remains limited regarding the effects of late ovarian hormone deprivation on cardiac fibrosis and ¿-adrenergic receptor expression in the context of SAH-an important gap considering the higher prevalence of SAH in women after midlife and the fact that they spend nearly one-third of their lives without ovarian hormonal protection. In this context, the present study aims to address these gaps by expanding current knowledge on the effects of late hormonal deprivation (a simulation of physiological menopause) in a setting of established SAH. Objective: To investigate whether late ovarian hormone deprivation in spontaneously hypertensive rats (SHR) leads to increased cardiac fibrosis and decreased expression of cardiac ¿-adrenergic receptors compared to normotensive rats (WKY, Wistar Kyoto), or whether aging is the predominant factor influencing such outcomes. Methods: Thirty-two female rats at 40 weeks of age will be divided into two groups (N=16): normotensive rats and spontaneously hypertensive rats. Each group will be further divided into two subgroups (N=8): one undergoing late ovarian hormone deprivation via bilateral ovariectomy (OVX), and the other undergoing sham surgery (SHAM). Both surgical procedures will be performed at 60 weeks of age. All animals will undergo the following evaluations: body mass assessment using a digital scale (at 40, 48, 56, 64, and 72 weeks of age); blood pressure measurement via tail-cuff plethysmography (at the same time points); quantification of cardiac ¿-adrenergic receptor gene expression by real-time polymerase chain reaction (RT-PCR); and histological analysis of cardiac tissue. For statistical analysis, data will be compiled in a spreadsheet and analyzed using Sigma-Stat® software, version 11.0. Differences will be considered statistically significant when p < 0.05.