Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure
Differential effects of angiotensin II versus endothelin-1 inhibitions in hypertrophic left ventricular myocardium during transition to heart failure
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DOI：
10.1161/hc3101.092201
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发表时间：
2001-07-31
期刊：
影响因子：
37.8
通讯作者：
Sasayama, S
中科院分区：
文献类型：
--
作者：
Iwanga, Y;Kihara, Y;Sasayama, S
背景-鉴于它们的相互串扰，血管紧张素II（Ang II）和内皮素-1（ET-1）在心肌中的作用被认为是协同和补充的。方法和结果-在Dahl盐敏感大鼠的代偿性左心室（LV）肥大阶段，Ang II肽和ACE mRNA在LV分别增加了1.6倍和3.8倍。相反，ET-1肽和preproET-1 mRNA保持不变。在随后的充血性心力衰竭（CBF），血管紧张素II和ACE mRNA没有显示进一步增加。但ET-1和mRNA从头分别增加了5.3倍和4.1倍。在升支大鼠中，局部激活的Ang II和ET-1也表现出不同的时间进程之间的左室肥厚和CHF。用替莫普利（一种ACE抑制剂）和波生坦（一种混合的ET受体阻滞剂）长期治疗达尔盐敏感大鼠同样改善了长期生存。Temocapril降低LV/体重比，改善LV缩短分数。相反，尽管波生坦同样改善了短轴缩短率，但并未减少LV质量的增加。与这2种药物的联合治疗进一步改善了动物的生存没有额外的收缩压降低。结论-在心肌的病理生理作用在过渡到CEF之间的Ang II和ET-1的性质不同。因此，ACE抑制和ET拮抗作用的组合的长期治疗可能为人类心力衰竭提供新的方法。
Background-In view of their mutual crosstalk, the roles of angiotensin II (Ang II) and endothelin-1 (ET-1) in the myocardium are assumed to be synergistic and supplemental.Methods and Results-In the phase of compensated left ventricular (LV) hypertrophy of Dahl salt-sensitive rats, Ang II peptide and the ACE mRNA in the LV were increased by 1.6- and 3.8-fold, respectively. In contrast, ET-1 peptide and the preproET-1 mRNA remained unchanged. In subsequent congestive heart failure (CBF), Ang II and ACE mRNA did not show further increases. But ET-1 and the mRNA were increased de novo by 5.3- and 4.1-fold, respectively. In ascending aorta-banded rats, the local activations of Ang II and ET-1 also showed a differential time course between LV hypertrophy and CHF. Long-term treatments of Dahl salt-sensitive rats with temocapril (an ACE inhibitor) and with bosentan (a mixed ET receptor blocker) equally improved long-term survival. Temocapril reduced the LV/body weight ratio and ameliorated LV fractional shortening. Conversely, although bosentan equally improved fractional shortening, it did not reduce the increase in LV mass. Combined treatment with these 2 drugs further ameliorated the animal's survival without additional decreases in systolic pressure.Conclusions-The pathophysiological roles in the myocardium during the transition to CEF differ qualitatively between Ang II and ET-1. Thus, long-term therapy with a combination of ACE inhibition and ET antagonism may provide a new approach for heart failure in humans.