Renin angiotensin and kallikrein kinin systems in hypertension, obesity, diabetes, desnutrition and sepsis: molecular, cellular and physiopathologic mechanisms

Abstract

The renin angiotensin system (RAS) is recognized as a powerful determinant of homeostasis and cardiovascular and renal hemodynamics. The relationship between the RAS physiology and renal and cardiovascular diseases is far from being understood. Cardiovascular diseases are responsible for high morbidity and mortality index in most countries. Among the various risk factors are the topics addressed in this project, namely, hypertension, obesity, diabetes. The influence of renin angiotensin system on the cardiovascular and renal functions is extremely complex, involving multiple mediators, receptors and different intracellular signaling mechanisms. This project aims to continue and to propose new studies about the role of this system in the pathophysiology of hypertension, obesity, diabetes, malnutrition and sepsis in the topics listed below: l) Markers of the Renin Angiotensin System in Hypertension and Obesity: The association between hypertension, obesity and diabetes is now a major public health problem. The knowledge of biological markers that can be used in the diagnosis and prognosis of these disease is extremely important for the development and improvement of prophylactic and therapeutic methods. Since the RAS is involved in cardiovascular and metabolic alterations evidenced in hypertensive, obese and diabetic patients, we aimed to evaluate the components of the RAS and their polymorphisms in hypertensive patients, obese children and children with low body weight at birth that is a risk for cardiovascular disease. In these studies we will also evaluate the presence of the N-domain ACE isoform with 90kDa, described as biological marker of hypertension; 2) Participation of the RAS in hypertension, diabetes, malnutrition and sepsis: physiologic mechanisms: Whereas animal models are an important experimental tool to complement the clinical and epidemiological studies in this topic, we different approaches; 4) Modulatory effects of exercise on hypertension and diabetes: considering the beneficial effects of exercise in the treatment of hypertension and diabetes we will study the modulatory effects of physical exercise on the Kallikrein-Kinin System and RAS in hypertensive patients, spontaneously hypertensive rats and rats previously exposed to malnutrition in utero. (AU)