Chaos and Arterial Remodelling in Resistant Hypertension (RHTN)

• Grant number: 23/10992-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Heitor Moreno Junior
• Grantee: Heitor Moreno Junior
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Moacir Fernandes de Godoy ; Tatiane de Azevedo Rubio

Abstract

Increased blood pressure (BP) levels are both the cause and the consequence of the hardening of large and medium-sized arteries, central, which is an important indicator of morbidity and mortality in several diseases, especially in Arterial Hypertension (AH). In this, stiffness results from remodeling of the arterial wall caused by biomechanical stimuli against biochemical, cellular and tissue, pro-inflammatory and proatherosclerotic mediators and modulators. Thus, together, these lead to differential gene and phenotypic expression ("remodeling") as well as concomitant alterations in the composition and stability of the arterial wall in the face of increasing parietal stress. Endothelial dysfunction (ED), increase in intima-media thickness (IMS), stiffness (stiffness) and consequent increase in pulse wave velocity (PWV) in large and medium-sized arteries then occur. Intermediate mechanisms from initial stimuli (arterial remodeling) to target organ damage (LOA) are well known in hypertension, especially in animal models of hypertension, as well as their early clinical expression (phenotype) by non-invasive methods in anima nobilis. Entretanto, this vascular remodelling does not follow the atherosclerotic (Dzau) and arteriosclerotic (O'Rourke) continuum models in Resistant Hypertension (RH). In these individuals, there are significant temporal oscillations of the BP variable with consequent variations in the prevalence of HR (detection, diagnosis), both complicated (cum plicate) and complex (cum plexuses) for interpretation by linear mathematics (deterministic modeling). In this project, knowledge about BP, the structure and function of vascular segments will be addressed as an essential introduction to the evolutionary development of arterial vessel remodeling in HR. Study design: This is an investigative study in resistant hypertensive patients, with the participation of 160 individuals, with a distribution of 40 / group: a) Normotensive: BP < 140 / 90 mmHg; b) Controlled Hypertensive: BP < 140 / 90 mmHg (under treatment with general measures, 1 or 2 antihypertensive drugs); c) Resistant Hypertensives and d) Refractory Hypertensives: according to AHA definitions in the body of the text. Individuals will be evaluated in 04 scheduled visits to HC-Unicamp with non-invasive hemodynamic parameters (blood pressure, peripheral vascular resistance and cardiac output) (Finometer), endothelial function test (Flow-Mediated Dilation, FMD), intima-media thickness (EMI, vascular US) and arterial stiffness (Complior, pulse wave velocity). We will apply the non-linear mathematical model of Chaos theory for the adjustment (fiting) of the data obtained, especially values of BP (office and ABPM) and arterial remodeling in subjects from the four experimental groups. It is intended to clarify the degree of participation of the variation and temporal variability of BP, HR and hemodynamic variables related to arterial remodeling in individuals with true HR as well as in pseudoresistant hypertension (white coat, masked and morning hypertension) in patients with adequate adherence to antihypertensive treatment. The knowledge generated will be able to change physiopathological concepts and the therapeutic action in true resistant hypertension (RH), allowing the reduction of pressure values and the stabilization of parietal stress and vascular remodeling in this condition. (AU)