Ricerc@Sapienza

The natriuretic peptides (NPs) play important functions within the cardiovascular system. Apart from maintaining blood pressure homeostasis, they exert anti-remodeling effects in both heart and vasculature. In particular, NPs are anti-hypertrophic in the heart. An increase of plasma NPs levels is a hallmark of heart failure (HF). Currently, a new therapeutic approach has been achieved by inhibition of NPs metabolism through neprilysin inhibition combined with AT1 receptor (AT1R) blockade (ARNi). This strategy allows an increase of circulating NPs and is currently indicated for the treatment of HF patients with reduced ejection fraction. Few preliminary studies have also shown that this therapeutic approach exerts positive effects in hypertension, one of the major causes of HF. With the current project we aim to study the impact of ARNi on cardiac remodeling in a rat model of hypertension, the stroke-prone spontaneously hypertensive rat (SHRSP), that develops several organ injuries including cardiac damage. We have recently shown that the administration of ARNi to SHRSP exerts protection from stroke and renal damage occurrence. In the current study, we will explore the ability of ARNi to prevent cardiac hypertrophy compared to AT1R blockade alone with valsartan and to valsartan plus hydrochlorothiazide. Moreover, we will test the potential ability of ARNi to induce regression of cardiac hypertrophy once it has been established. The cardiac phenotype will be evaluated by means of echocardiography and also by histological and molecular analyses (markers of oxidative stress, inflammation and fibrosis).
Evidence of reduced cardiac hypertrophy and of reduced remodeling obtained upon treatment with ARNi compared to valsartan alone and to valsartan plus diuretic in SHRSP rats will represent the optimal basis for larger clinical studies aimed at evaluating cardiac damage protection under combination of neprilysin inhibition and AT1R blockade in human hypertension.