González Jaime, Valls Nicolás, Brito Roberto, Rodrigo Ramón
Jaime González, Nicolás Valls, Roberto Brito, Ramón Rodrigo, Laboratory of Oxidative Stress and Nephrotoxicity, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70058, Chile.
World J Cardiol. 2014 Jun 26;6(6):353-66. doi: 10.4330/wjc.v6.i6.353.
Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.
原发性高血压是一种高度普遍的病理状态,被认为是最相关的心血管危险因素之一,也是全球发病和死亡的重要原因。尽管高血压的潜在机制尚未完全阐明,但大量证据表明氧化应激在其病理生理学中起核心作用。氧化应激可定义为氧化剂(如超氧阴离子)与抗氧化分子之间的失衡,并导致一氧化氮生物利用度降低,而一氧化氮是维持血管张力的主要因素。几种血管收缩肽,如血管紧张素II、内皮素-1和尾加压素II,通过其受体发挥作用,通过激活NADPH氧化酶和黄嘌呤氧化酶等酶来刺激活性氧的产生。基于上述机制的认识,已开发出基于使用抗氧化剂的抗高血压新治疗策略,包括维生素C和E、N-乙酰半胱氨酸、多酚和硒等。这些物质有不同的治疗靶点,但都代表抗氧化增强作用。已经进行了几项使用抗氧化剂的临床试验。本综述的目的是提供关于氧化应激在原发性高血压病理生理学中的关键作用的新见解,以及证明抗氧化治疗在高血压治疗中的有效性的新临床尝试。