New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension.
Elevated production of prostanoids from the constitutive (COX-1) or inducible (COX-2) cyclo-oxygenases has been involved in the alterations in vascular function, structure and mechanical properties observed in cardiovascular diseases, including hypertension. In addition, it is well known that production of ROS (reactive oxygen species) plays an important role in the impaired contractile and vasodilator responses, vascular remodelling and altered vascular mechanics of hypertension. Of particular interest is the cross-talk between NADPH oxidase and mitochondria, the main ROS sources in hypertension, which may represent a vicious feed-forward cycle of ROS production. In recent years, there is experimental evidence showing a relationship between ROS and COX-derived products. Thus ROS can activate COX and the COX/PG (prostaglandin) synthase pathways can induce ROS production through effects on different ROS generating enzymes. Additionally, recent evidence suggests that the COX-ROS axis might constitute a vicious circle of self-perpetuating vasoactive products that have a pathophysiological role in altered vascular contractile and dilator responses and hypertension development. The present review discusses the current knowledge on the role of oxidative stress and COX-derived prostanoids in the vascular alterations observed in hypertension, highlighting new findings indicating that these two pathways act in concert to induce vascular dysfunction.
*Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, Alcorcón, Spain.
Raquel
R
Hernanz
Ana M
AM
Briones
Mercedes
M
Salaices
María J
MJ
Alonso
D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D011453:Prostaglandins; D017382:Reactive Oxygen Species; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019255:NADPH Oxidases