Sacubitril/Valsartan Reduced Pulmonary Hypertension and Right Heart Damage in Rats

Pulmonary hypertension was induced in Sprague-Dawley rats using the SU5416/hypoxia model. Animals were divided into four groups: normoxic controls (n=18), PH with placebo (n=34), PH with sacubitril/valsartan (n=24), and PH with valsartan alone (n=16). Treatment lasted six weeks. Outcomes included right ventricular pressure, hypertrophy index, collagen content, contractility, pulmonary vascular wall thickness, natriuretic peptide levels, and PKC isozyme expression.

Pulmonary hypertension remains difficult to treat, and the right ventricle's response to it is a major driver of patient outcomes. Sacubitril/valsartan (marketed as Entresto) is already widely used for left-sided heart failure. This study suggests it could potentially be repurposed for pulmonary hypertension by leveraging its unique dual mechanism — blocking angiotensin while simultaneously preserving natriuretic peptides that naturally dilate lung blood vessels.

This study connects two major peptide systems — natriuretic peptides (ANP/BNP) and the renin-angiotensin system — in the context of pulmonary hypertension. By showing that preserving natriuretic peptides through neprilysin inhibition adds benefit beyond angiotensin blockade alone, it supports the growing view that targeting peptide degradation pathways is a viable therapeutic strategy. Clinical trials testing sacubitril/valsartan in human pulmonary hypertension are an important next step.

This is an animal study using a specific rat model (SU5416/hypoxia) that mimics some but not all features of human pulmonary arterial hypertension. The six-week treatment duration may not capture long-term effects. Group sizes were unequal (16–34 per group). Results in rats may not translate directly to humans due to differences in drug metabolism, hemodynamics, and disease complexity. The study did not assess survival outcomes.