Oxidant and redox signaling in vascular oxygen sensing: implications for systemic and pulmonary hypertension.
It has been well known for >100 years that systemic blood vessels dilate in response to decreases in oxygen tension (hypoxia; low PO2), and this response appears to be critical to supply blood to the stressed organ. Conversely, pulmonary vessels constrict to a decrease in alveolar PO2 to maintain a balance in the ventilation-to-perfusion ratio. Currently, although little question exists that the PO2 affects vascular reactivity and vascular smooth muscle cells (VSMCs) act as oxygen sensors, the molecular mechanisms involved in modulating the vascular reactivity are still not clearly understood. Many laboratories, including ours, have suggested that the intracellular calcium concentration ([Ca2+]i), which regulates vasomotor function, is controlled by free radicals and redox signaling, including NAD(P)H and glutathione (GSH) redox. In this review article, therefore, we discuss the implications of redox and oxidant alterations seen in pulmonary and systemic hypertension, and how key targets that control [Ca2+]i, such as ion channels, Ca2+ release from internal stores and uptake by the sarcoplasmic reticulum, and the Ca2+ sensitivity to the myofilaments, are regulated by changes in intracellular redox and oxidants associated with vascular PO2sensing in physiologic or pathophysiologic conditions.
Gupte
Sachin A
SA
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA. sachin_gupte@nymc.edu
Wolin
Michael S
MS
D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000503:physiopathology; D015398:Signal Transduction; D014661:Vasoconstriction
D016877:Oxidants; D010100:Oxygen