Ibarra-Lara Luz, Sánchez-Aguilar María, Hong Enrique, del Valle-Mondragón Leonardo, Soria-Castro Elizabeth, Pérez-Severiano Francisca, Torres-Narváez Juan Carlos, Ramírez-Ortega Margarita, Pastelín-Hernández Gustavo S, Cervantes-Pérez Luz G, Sánchez-Mendoza Alicia
*Department of Pharmacology, National Institute of Cardiology "Ignacio Chávez," Mexico City, Mexico; †Department of Neuropharmacology and Experimental Therapeutics, Research and Advanced Studies Center of the National Polytechnic Institute (CINVESTAV-IPN), Mexico City, Mexico; ‡Department of Pathology, National Institute of Cardiology "Ignacio Chávez" Mexico City, Mexico; and §Department of Neurochemistry, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez," Mexico City, Mexico.
J Cardiovasc Pharmacol. 2015 May;65(5):430-7. doi: 10.1097/FJC.0000000000000186.
We have recently demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) 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 PPARα 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 PPARα 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 PPARα by clofibrate prevents an increase in the activity of renin-angiotensin system and promotes the production of vasodilator substances.
我们最近证明，过氧化物酶体增殖物激活受体α（PPARα）刺激可降低心脏和血浆中血管紧张素II的生成，同时增加血管紧张素-(1-7)的生成。这种刺激可改善一氧化氮的生物利用度，保持心脏的组织学特征和功能。基于这些结果，我们决定研究PPARα刺激对缺血心肌肾素-血管紧张素系统成分的影响。将雄性Wistar大鼠（体重300-350克）分为以下几组：（1）假手术组，（2）心肌缺血溶剂处理组（MI-V），（3）心肌缺血氯贝丁酯处理组。缺血期间血管紧张素转换酶的表达增加，而氯贝丁酯处理组与对照组相当。PPARα受体的激活刺激了血管紧张素转换酶-2的表达；虽然该酶的活性在MI-V组中增加，但氯贝丁酯抑制了任何变化。用该药物处理的动物匀浆中缓激肽和磷酸化Akt（SER473）的浓度增加。MI-V大鼠中Mas受体表达增加。总之，氯贝丁酯刺激PPARα可防止肾素-血管紧张素系统活性增加，并促进血管舒张物质的产生。
