Author(s): VELASCO, T., AGUILAR, B.A., DALVIT, L.F., BERNAL, J.V.M., LAVEZ, G., AZARIAS, A., SOUZA, H.C.D., Institution: UNIVERSITY OF SAO PAULO - FACULTY OF MEDICINE OF RIBEIRÃO PRETO, Country: BRAZIL, Abstract-ID: 2525

INTRODUCTION:
Systemic arterial hypertension (SAH) is highly prevalent in adults and may lead to cardiac dysfunction and heart failure if left untreated. Its management includes different classes of antihypertensive drugs as well as lifestyle modifications, such as regular physical exercise. Experimental studies have shown that AT₁ receptor blockade effectively reduces blood pressure but exerts limited effects on cardiac contractility, whereas aerobic exercise training (AET) enhances myocardial function. In contrast, combined inhibition of AT₁ receptors (valsartan) and neprilysin (sacubitril) has demonstrated significant benefits on cardiac performance, including increased ejection fraction in patients with heart failure. However, its effects in hypertensive conditions remain poorly understood. The aim of this study was to investigate the effects of combined valsartan/sacubitril therapy on left ventricular (LV) contractility in spontaneously hypertensive rats (SHR) and to determine whether AET provides additional functional benefits.
METHODS:
Male SHR (N = 64), aged 18 weeks, were allocated into four groups (N = 16 per group) according to a 12-week treatment protocol: Vehicle; Valsartan (30 mg·kg⁻¹·day⁻¹); Valsartan (30 mg·kg⁻¹·day⁻¹) + hydrochlorothiazide (10 mg·kg⁻¹·day⁻¹); and Valsartan (30 mg·kg⁻¹·day⁻¹) + sacubitril (28 mg·kg⁻¹·day⁻¹). Half of each group (N = 8) underwent AET for 12 weeks. Hemodynamic parameters were assessed at baseline (18th week) and at the end of the protocol (30th week). LV contractility was evaluated at week 30 using the isolated heart Langendorff technique.
RESULTS:
All valsartan-treated groups showed significant reductions in blood pressure (BP) and heart rate (HR) compared with the Vehicle group. Among trained animals, only the Vehicle group exhibited additional reductions in BP and HR. In non-trained groups, only the Valsartan/Sacubitril group demonstrated increased LV contractility (P < 0.002), dP/dt_max (P < 0.020), and dP/dt_min (P < 0.001). However, no differences in LV contractility (P < 0.463), dP/dt_max (P < 0.168), or dP/dt_min (P < 0.780) were observed among trained groups.
CONCLUSION:
Neprilysin inhibition increases cardiac contractility in hypertensive rats, whereas AT₁ receptor blockade alone appears to attenuate contractile performance. Aerobic exercise training does not further potentiate the effects of neprilysin inhibition but plays a critical role in preserving cardiac contractility when combined with AT₁ receptor blockade.