Abstract 17134: Angiotensin II Receptor Blocker And Neprilysin Inhibitor Sacubitril/valsartan Attenuates Experimental Pulmonary Hypertension

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A17134-A17134
• Main Authors: Clements, Richard T, Vang, Alexander, Kue, Nouaying R, Mancini, Thomas, Morrison, Alan R, McCullough, Danielle J, Mallem, Krishna, Choudhary, Gaurav
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.17134

IntroductionThe neprilysin inhibitor and angiotensin receptor blocker sacubitril/valsartan (Sac/Val, LCZ696) was recently approved for treatment of left heart failure (HFrEF). However, little is known if this drug treatment may be beneficial in right ventricular (RV) hypertrophy and failure associated with pulmonary hypertension (PH). Angiotensin II has been implicated in the development of maladaptive RV hypertrophy and fibrosis associated with PH. Natriuretic peptides promote pulmonary vasodilation, inhibit vascular remodeling and thereby decrease RV afterload, but are quickly degraded by neprilysin.HypothesisSac/Val will attenuate PH and improve RV function by targeting both pulmonary vascular and RV remodeling.MethodsPAH was induced in rats using SU5416/hypoxia (SUH), followed by 6-week treatment with placebo, Sac/Val, or Val alone. There were 4 groupsCON - normoxic rats with placebo; PH - SUH rats + placebo; PH + Sac/Val; and PH + Val (minimum n=16 in each group). RV and LV function was measured by echocardiography before and after treatment followed by sacrifice at 6 weeks when RV hypertrophy, pulmonary vessel muscularity, and tissue and serum natriuretic peptides and cGMP levels were evaluated. One Way ANOVA, SNK post-hoc test was used to determine significance.ResultsBefore treatments, all SUH animals had changes consistent with PH including increased RV pressures (P