HEMODYNAMIC, MORPHOLOGICAL AND FUNCTIONAL HEART ADAPTATIONS IN HYPERTENSIVE RATS - EFFECT OF OVARIAN HORMONE DEPRIVATION.

• Grant number: 22/11615-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: September 30, 2024
• 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
• Associated scholarship(s): 23/12994-2 - Improving Blood Pressure and Cardiovascular Risk with Resistance Exercise in African Americans, BE.EP.IC

Abstract

Introduction: Introduction: The significant reduction in ovarian hormones, which results in menopause, increases the risk of developing cardiovascular diseases that affect cardiac and vascular morphology and functionality. However, some women already have an underlying cardiovascular disease even before menopause, such as systemic arterial hypertension (SAH). In this case, ovarian failure in these women can trigger even more severe morphological and functional cardiac and vascular damage. However, the mechanisms involved in these processes are not well defined. Our hypothesis is that the increase in fibrosis, and consequently, the morphological and functional cardiac impairments involve the participation of calpain-1 and metalloproteinase-2 (MMP-2). Objectives: To investigate in spontaneously hypertensive rats (SHR; spontaneously hypertensive rats) the effects of ovarian failure on hemodynamics, coronary bed reactivity and left ventricular contractility, as well as the participation of intracellular mechanisms of the proteolytic targets of calpain-1 and MMP-2. Methods: 64 rats at 18 weeks of age will be divided equally into two large groups; normotensive (Wistar-Kyoto) and hypertensive (SHR, spontaneously hypertensive rats). Each group will be subdivided into two smaller groups (N=16); ovariectomized group at 18 weeks of life (OVX); and group submitted to sham surgery (SHAM) also in the 18th week of life. Both groups will be submitted to the following experimental protocols; hemodynamic assessment at four different moments by means of plethysmography (18th, 22nd, 28th and 34th weeks of life); echocardiographic assessment of cardiac morphology and functionality at the 18th and 34th weeks of life; assessment of cardiac function and coronary reactivity in an isolated heart using the Langendorff technique; and evaluation of calpain-1 and MMP-2 activities. The results of the present study will contribute to the understanding of the mechanisms involved in adverse cardiac morphofunctional adaptations resulting from the deprivation of ovarian hormones associated with SAH.