Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure.

Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Research Abstract Details 

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Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Abstract Text:

Qin-gui Xia,Alexander Reinecke,Marc Dorenkamp,Mat Jap Daemen,Reichiger Simon,Thomas Unger,Qin-gui Xia,Alexander Reinecke,Marc Dorenkamp,Mat Jap Daemen,Reichiger Simon,Thomas Unger,

AIM: To investigate whether the endothelin ETA receptor blocker provides similar benefit on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure (CHF). METHODS: Male stroke-prone spontaneously hypertensive (SHR-SP) rats were subjected to permanent ligation of the left coronary artery and were treated for 6 weeks with the endothelin ETA receptor blocker LU 135252 (30 mg.kg(-1).d(-1)) starting 24 h after ligation or untreatment. Sham-operated rats served as normal controls. The mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular contractility (LV dp/dt(max)), left ventricular inner diameter (LVD) and circumference (LVC), septal thickness, left ventricular interstitial collagen content (ICC) and heart weight (HW) were measured at the end of the treatment. RESULTS: Compared with the untreated group, LU 135252 tended to increase HW (1.43 +/-0.03 vs 1.38 +/-0.04 g; P> 0.05), increased LVD (7.65+/-0.24 mm vs 6.58+/-0.14 mm; P<0.05), markedly increased LVC (30.11+/-0.83 mm vs 24.82+/-0.85 mm; P< 0.01) and reduced left ventricular ICC (3.79%+/-0.09% vs 6.71%+/-0.11%; P< 0.01), slightly lowered MAP (132+/-6 mmHg vs 142+/-4 mmHg; P>0.05), reduced LVEDP (14 4 mmHg vs 27+/-4 mmHg; P<0.05) and improved LV dp/dtmax (4230+/-450 mmHg/s vs 1950+/-400 mmHg/s; P<0.05); survival was not prolonged significantly (13% vs 11%; P=NS). CONCLUSION: In this hypertensive rat model of CHF, chronic endothelin ETA receptor blockade with LU 135252 improves cardiac hemodynamics, however, it does not affect long-term survival and worsens cardiac remodeling. Thus, endothelin ETA receptor antagonists are unlikely to have an important role in the management of patients with CHF.

Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Publishing Authors By Initials

QG Xia,A Reinecke,M Dorenkamp,MJ Daemen,R Simon,T Unger,QG Xia,A Reinecke,M Dorenkamp,MJ Daemen,R Simon,T Unger,

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Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Acta pharmacologica Sinica

VOLUME: 27

Page Numbers: 1417-22

Journal Abbreviation: Acta Pharmacol. Sin.

ISSN: 1671-4083

DAY: 19

MONTH: Nov

YEAR: 2006

Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure.

AFFILIATION: Department of Physiology, Wenzhou Medical College, Wenzhou 325027, China. xqg@wzmc.net

Country: China

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MEDLINETA: Acta Pharmacol Sin

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