title: Chronic antioxidant therapy fails to ameliorate hypertension: potential mechanisms behind.
abstract: Hypertension in association with oxidative stress belongs to the most discussed topics within the literature on cardiovascular diseases. It is generally believed that elevated production of reactive oxygen species (ROS) plays an important role in hypertension, but clinical studies on chronic antioxidant therapy of hypertension fail to confirm this hypothesis. This discrepancy may be partly determined by the different effects of short and long-lasting treatment with antioxidants or scavengers. Elevated ROS production in hypertension need not be only harmful. It may also stimulate the activity of the antioxidant defence system and improve the nitric oxide (NO)/cyclic 3', 5'-guanosine monophosphate pathway, resulting in the establishment of a new equilibrium between enhanced oxidative load and the stimulated NO pathway, thus maintaining sufficient NO bioavailability. It has been suggested that antioxidant treatment might be beneficial for a short time, until increased NO generation predominates over ROS production. Further weakening of ROS formation by antioxidants may attenuate nuclear factor kappa B activation resulting in decreased endothelial NO synthase expression and activity. Prolonged antioxidant therapy may thus attenuate the beneficial regulatory effect of ROS, leading to decreased NO generation and the re-establishment of the undesirable disproportion between deleterious and protective forces. As a consequence prolonged antioxidant treatment in human hypertension may fail to provide the expected clinical profit.
authors.affiliation: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences and Center of Excellence for Cardiovascular Research, Bratislava, Slovak Republic. olga.pechanova@savba.sk
authors.forename: Olga
authors.initials: O
authors.lastname: Pechanova
authors.forename: Fedor
authors.initials: F
authors.lastname: Simko
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000628:therapy*; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester