Departamento de Fisiología y Zoología, Universidad de Sevilla, Spain.
Eur J Pharmacol. 2010 Apr 25;632(1-3):65-72. doi: 10.1016/j.ejphar.2010.01.017. Epub 2010 Feb 1.
It has been shown that oxidative stress is involved in the pathogenesis of arterial hypertension. The aim of this work was to study and compare the molecular mechanisms of the antioxidant properties of l-carnitine and captopril in spontaneously hypertensive rats (SHR). Antioxidant enzyme activity/regulation (glutathione peroxidase, glutathione reductase and superoxide dismutase) was measured in the erythrocytes and hearts of SHR. The molecular expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase, angiotensin converting enzyme (ACE), angiotensin II type I receptor (AT(1) receptor) and NF-kappaB/IkappaB system was also measured in the hearts of these animals. Both l-carnitine and captopril augmented the antioxidant defense capacity in SHRs. This effect was mediated by an upregulation of antioxidant enzymes, an increase in the plasma total antioxidant capacity and a reduction of lipid peroxidation and superoxide anion production in the heart. The administration of both compounds to hypertensive animals also produced an upregulation of eNOS and a normalization of ACE, angiotensin AT(1) receptor, and the NF-kappaB/IkappaB system expression. In addition, captopril reduced the arterial blood pressure and the relative heart weights back to control values, whereas l-carnitine caused only a partial reduction of blood pressure values and did not alter the cardiac hypertrophy found in SHRs. In conclusion, we have found that l-carnitine and captopril have a similar antioxidant effect in the hearts of hypertensive rats. The molecular regulation of antioxidant enzymes through an inhibition of the renin-angiotensin system and a modulation of the NF-kappaB/IkappaB system seems to be responsible for this antioxidant effect.
已经表明氧化应激参与了动脉高血压的发病机制。本工作的目的是研究和比较左旋肉碱和卡托普利在自发性高血压大鼠（SHR）中的抗氧化特性的分子机制。在 SHR 的红细胞和心脏中测量抗氧化酶活性/调节（谷胱甘肽过氧化物酶、谷胱甘肽还原酶和超氧化物歧化酶）。还在这些动物的心脏中测量内皮型一氧化氮合酶（eNOS）、NADPH 氧化酶、血管紧张素转换酶（ACE）、血管紧张素 II 型 1 型受体（AT1 受体）和 NF-κB/IκB 系统的分子表达。左旋肉碱和卡托普利均可增强 SHR 的抗氧化防御能力。这种作用是通过抗氧化酶的上调、血浆总抗氧化能力的增加以及心脏中脂质过氧化和超氧阴离子产生的减少来介导的。这两种化合物在高血压动物中的给药也导致 eNOS 的上调和 ACE、血管紧张素 AT1 受体和 NF-κB/IκB 系统表达的正常化。此外，卡托普利将动脉血压和相对心脏重量降低到对照值，而左旋肉碱仅导致血压值的部分降低，并且不改变 SHR 中发现的心脏肥大。总之，我们发现左旋肉碱和卡托普利在高血压大鼠的心脏中具有相似的抗氧化作用。通过抑制肾素-血管紧张素系统和调节 NF-κB/IκB 系统来调节抗氧化酶的分子调节似乎是这种抗氧化作用的原因。
