Abstract
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/dtmax), 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.
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Project supported by grant from the German Institute of High Blood Pressure, Heideburg, Germany.
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Xia, Qg., Reinecke, A., Dorenkamp, M. et al. Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure. Acta Pharmacol Sin 27, 1417–1422 (2006). https://doi.org/10.1111/j.1745-7254.2006.00447.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00447.x
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