Oxidative Stress in Hypertension: Mechanisms and Therapeutic Opportunities

Abstract

Artículo de publicación ISISin acceso a texto completoHypertension is a highly prevalent disease worldwide. It is known for being one of the most important risk factors for developing cardiovascular disease, including acute myocardial infarction and stroke. Therefore, during the last decades there have been multiple efforts to fully understand the mechanisms underlying hypertension, and then develop effective therapeutic interventions to attenuate the morbidity and mortality associated with this condition. In this regard, oxidative stress has been proposed as a key mechanistic mediator of hypertension, which is an imbalance between oxidant species and the antioxidant defense systems. A large amount of evidence supports the role of vascular wall as a major source of reactive oxygen species. These include the activation of enzymes, such as NADPH oxidase and xanthine oxidase, the uncoupling eNOS and mitochondrial dysfunction, having as a major product the superoxide anion. Among the stimuli that increase the production of oxidative species can be found the action of some vasoactive peptides, such as angiotensin II, endothelin-1 and urotensin II. The oxidative stress state generated leads to a decrease in the biodisponibility of nitric oxide and prostacyclin, key factors in maintaining the vascular tone. The knowledge of the mechanisms mentioned above has allowed generating some therapeutic strategies using antioxidants as antihypertensives with different results. Further studies are required to position antioxidants as key agents in the treatment of hypertension. The current review summarize evidence of the role of oxidative stress in hypertension, emphasizing in therapeutic targets that can be consider in antioxidant therapy

The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory

“…In animal models, CGRP, eNOS, and serotonin each protect against the development of hypertension. However, oxidative stress, a likely aspect of migraine vulnerability, is a risk factor for hypertension, endothelial dysfunction, and atherosclerosis …”

Angeli's Salt, a nitroxyl anion donor, reverses endothelin-1 mediated vascular dysfunction in murine aorta

“…Using DHE staining for ROS generation, we observed an increase in ET - 1 - mediated ROS production in primary VSMCs. ROS is a known contributor to vascular dysfunction, and is present during hypertension and other cardiovascular disease (Gonzalez et al , 2014; Brito et al , 2015). We hypothesized that Gtn, or NO as a free radical gas, may interact with the ET-1-induced ROS present, further increasing the oxidant environment.…”

“…Common mediators of hypertension-induced ROS generation, promotion of oxidative stress and vascular wall damage are angiotensin II (AngII) and endothelin-1 (ET-1) (Wilcox, 2002; Palm et al , 2010; Wilcox, 2010; Pollock & Pollock, 2011; Nguyen Dinh C at et al , 2013; Gonzalez et al , 2014; Brito et al , 2015; Montezano et al , 2015 ). In this manuscript, we sought to determine whether the HNO/NO − donor (AS) would alleviate ET-1-induced vascular dysfunction.…”

Polymorphisms in NADPH oxidase CYBA gene modify the risk of ESRD in patients with chronic glomerulonephritis

“…20,21 However, it has not been clearly shown whether oxidative stress exacerbates renal damage in patients with chronic renal failure. Nowadays, the central role of NADPH oxidase both in experimental and human cardiovascular diseases, such as metabolic syndrome, 22 hypertension, 23 NADPH oxidase is sensitively regulated by a wide range of (patho) physiologically relevant factors, which include the following: (i) humoral factors, (ii) mechanical factors and (iii) genetic variants. 28,29 CYBA is an important subunit of the NADH/NADPH oxidase.…”