Prevention of diastolic heart failure by endothelin type A receptor antagonist through inhibition of ventricular structural remodeling in hypertensive heart

Journal of Hypertension
Kazuhiro YamamotoMasatsugu Hori

Abstract

Despite the clinical frequency of diastolic heart failure, its therapeutic strategy has not been established. Our recent study demonstrated activation of the endothelin (ET) system in a diastolic heart failure model with hypertension. Several studies have reported that ET type A (ETA) receptor antagonist improves systolic function and prevents systolic heart failure; however, its effects on diastolic heart failure are unknown. We investigated the effects of chronic administration of ET(A) receptor antagonist in diastolic heart failure. Dahl-Iwai salt-sensitive rats fed on a high-salt diet from 7 weeks of age, in which congestive heart failure develops following hypertension without cardiac chamber dilatation or systolic dysfunction, were divided into groups with and without administration of a subdepressor dose of ET(A) receptor antagonist. Hypertension induced compensatory left ventricular (LV) hypertrophy at 13 weeks in six untreated rats. Persistent pressure overload developed progressive LV hypertrophy and fibrosis from 13 to 19 weeks, resulting in elevated LV filling pressure and increased lung weight. Chronic ET(A) receptor blockade did not restrain compensatory LV hypertrophy at 13 weeks; however, it attenuated LV hypert...Continue Reading

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Citations

Jul 8, 2003·Current Hypertension Reports·Rubin ZhangEfrain Reisin
Oct 20, 2005·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hisashi KaiTsutomu Imaizumi
Aug 14, 2012·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·James C FangRaymond L Benza
Jan 13, 2004·Journal of the American College of Cardiology·Hitoshi YamaguchiTohru Masuyama
Jun 26, 2004·Current Opinion in Cardiology·Joanne MoncrieffFrancis G Dunn
May 31, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Anja-Kristin SiegelReinhold Kreutz
Mar 22, 2008·Journal of Cardiovascular Pharmacology·Shigefumi FukuiHiroaki Shimokawa

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