The Effect Of The Non-Selective En-dothelin Receptor Antagonist TAK-044 On Cardiac Remodeling

Objective To investigate the relationship between endothelin(ET) and hypertensive cardiac remodeling, the effect of the non-selective endothelin receptor antagonist TAK-044 on cardiac remodeling were evaluated.Methods TAK-044 was administered intraperitoneally (10 mg · kg-1 · day-1) into 10 male spontaneously hypertension rats (SHR) for 6 weeks from 10 weeks of age. Another 10 Sex,age and body weight matched untreated SHR and 10 WKY rats served as controls( saline was given, 1 ml · kg-1 · day-1). Systolic blood pressure (SBP), body weight(BW) were measured once a week. All the animals were killed after six weeks, left ventricular mass (LVM) and left ventricular mass index (LVMI) were determined. Car-diomyocytes size, collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed with computed video processing.Results The SBP, LVM, LVMI, Cardiomyocytes size, collagen volume fraction (CVF) and perivascular collagen area (PVCA) were significantly increased in treated SHR compared with WKY rats. SBP were significantly reduced but could not restore to normal level in TAK-044 treated SHR group. TAK-044 could decreased the degree of left ventricular hypertrophy and PVCA, but have no influence on CVF.Conclusion Endothelins take part in the procedure of cardiac remodeling in hypertension, and endothelin receptor antagonist TAK-044 can decrease the degree of cardiac remodeling and SHR's blood pressure.