Study of the Effects of Neprilysin Inhibition on Cardiac Function in Hypertensive Rats—Isolated Heart Study

Background/Objectives: Valsartan/sacubitril improves outcomes in heart failure, but its effects on cardiac performance in chronic hypertension remain unclear. We investigated the effects of chronic valsartan/sacubitril treatment on hemodynamics, cardiac morphology and function, coronary perfusion pressure, and left ventricular responses in spontaneously hypertensive rats (SHR). Methods: Thirty-two male SHR were assigned to Vehicle, Valsartan, Valsartan/Hydrochlorothiazide, or Valsartan/Sacubitril groups (n = 8) and treated for 12 weeks. Hemodynamic and echocardiographic parameters were assessed at 18 and 30 weeks of age. At 30 weeks, isolated-heart responses to progressive increases in coronary flow and to β-adrenergic stimulation were evaluated using the Langendorff technique. Results: All pharmacological treatments reduced blood pressure versus Vehicle, with no additional reduction from combination therapy compared with Valsartan alone. Echocardiographic parameters showed time-related changes without treatment-specific effects. At the highest coronary flow levels, Valsartan/Sacubitril preserved left ventricular pressure and showed greater dP/dtmax and more negative dP/dtmin values than all other groups. β-Adrenergic responsiveness also differed among groups, particularly at higher agonist doses. Conclusions: In SHR, all pharmacological treatments reduced blood pressure to a similar extent, with no additional reduction when valsartan was combined with hydrochlorothiazide or sacubitril. In the isolated heart, however, only valsartan/sacubitril maintained left ventricular contractile performance.