PPARα Stimulation Modulates Myocardial Ischemia-induced Activation of Renin-Angiotensin System
PPARα Stimulation Modulates Myocardial Ischemia-induced Activation of Renin-Angiotensin System
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DOI：
10.1097/fjc.0000000000000186
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发表时间：
2015-05-01
影响因子：
3
通讯作者：
Sanchez-Mendoza, Alicia
中科院分区：
文献类型：
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作者：
Ibarra-Lara, Luz;Sanchez-Aguilar, Maria;Sanchez-Mendoza, Alicia
我们最近证实，在心脏和血浆水平，PPARα的刺激降低了血管紧张素II的产生，而增加了Ang-(1-7)的产生。这种刺激提高了一氧化氮的生物利用度，保留了心脏的组织学特征和功能。基于这些结果，我们决定研究刺激PPARα对缺血心肌肾素血管紧张素系统成分的影响。雄性Wistar大鼠(体重300~350g)分为假手术组、心肌缺血剂(MI-V)组和氯贝特组。血管紧张素转换酶在缺血期间的表达增加，而氯贝特组的表达与对照组相当。激活PPARa受体刺激血管紧张素转换酶-2的表达；而在MI-V中该酶的活性增加，氯贝特抑制任何变化。用药后，动物匀浆中缓激肽和磷酸化Akt(SER473)的浓度增加。MI-V大鼠MAS受体表达增加。结论：氯贝特刺激PPARa可阻止肾素血管紧张素系统活性的增加，并促进血管扩张物质的产生。
We have recently demonstrated that peroxisome proliferator activated receptor alpha (PPAR alpha) stimulation lowers the production of angiotensin II while increasing the production of Ang-(1-7), both in cardiac and plasmatic level. This stimulation improves nitric oxide bioavailability, preserving cardiac histologic features and functioning. Based on these results, we decided to study the effect of PPAR alpha stimulation on renin angiotensin system components of ischemic myocardium. Male Wistar rats (weighing 300-350 g) were assigned to the following groups: (1) sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate treated. Expression of the angiotensin-converting enzyme increased during ischemia, whereas clofibrate-treated group remained comparable to control. Activation of the PPARa receptor stimulated the expression of angiotensin-converting enzyme-2; while the activity of this enzyme was increased in MI-V, clofibrate inhibited any change. The concentration of bradykinin and phospho-Akt(SER473) in homogenate increased in the animals treated with the drug. Mas receptor expression increased in MI-V rats. In conclusion, stimulation of PPARa by clofibrate prevents an increase in the activity of renin angiotensin system and promotes the production of vasodilator substances.