Reactive oxygen species and the control of vascular function

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Abstract
This article summarizes perspectives on how reactive oxygen species (ROS) and redox signaling mechanisms participate in regulating vascular smooth muscle function that have resulted from our studies over the past 25 years in areas including oxygen sensing and the regulation of cGMP production by soluble guanylate cyclase (sGC) that were presented in the Robert M. Berne Distinguished Lectureship at the 2008 Experimental Biology Meeting. It considers mechanisms controlling the activity of sources of ROS including Nox oxidases and mitochondria by physiological stimuli, vascular diseases processes, and metabolic mechanisms linked to NAD(P)H redox and hypoxia. Metabolic interactions of individual ROS such as hydrogen peroxide with cellular peroxide metabolizing enzymes are viewed as some of the most sensitive ways of influencing cellular signaling systems. The control of cytosolic NADPH redox also seems to be a major contributor to bovine coronary arterial relaxation to hypoxia, where its oxidation functions to coordinate the lowering of intracellular calcium, whereas increased cytosolic NADPH generation in pulmonary arteries appears to maintain elevated Nox oxidase activity, and relaxation to hydrogen peroxide, which is attenuated by hypoxia. The sensitivity of sGC to nitric oxide seems to be regulated by thiol and heme redox systems controlled by cytosolic NADPH. Heme biosynthesis and metabolism are also important factors regulating the sGC system. The signaling pathways controlling oxidases and their colocalization with redox-regulated systems enables selective activation of numerous regulatory mechanisms influencing vascular function in physiological processes and the progression of aging-associated vascular diseases.

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