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(Circulation. 2008;117:594-597.)
© 2008 American Heart Association, Inc.

Editorial

Evidence Mounts That Nitrite Contributes to Hypoxic Vasodilation in the Human Circulation

Mark T. Gladwin, MD

From the Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, and the Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md.

Correspondence to Mark T. Gladwin, MD, Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10-CRC, Room 5-5140, 10 Center Dr, MSC 1454, Bethesda, MD 20892-1454. E-mail mgladwin@nih.gov

Key Words: Editorials • hemoglobin • nitric oxide • vasodilation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Hypoxic vasodilation is a conserved physiological response to hypoxia that matches blood flow and oxygen delivery to tissue metabolic demand. This fundamental physiological process has been characterized for >100 years since the initial description by Roy and Brown¹ in 1880. Hypoxic vasodilation requires a sensor mechanism that can detect a divergence in the normal relationship between delivered blood oxygen and tissue oxygen consumption.² This hypoxic sensor mechanism must be coupled to the feedback generation of vasodilatory effectors that increase blood flow to maintain adequate tissue oxygenation. In short, hypoxic vasodilation requires hypoxia and/or pH sensing coupled to the release of a vasodilating signal. In mammalian species, the set point for hypoxic vasodilation occurs as the hemoglobin desaturates from 60% to 40%, around a partial pressure of oxygen ranging from 40 to 20 mm Hg.³ Despite the fact that the hypoxic vasodilation response was discovered almost 150 years ago, the identities of the oxygen sensor mechanism and the specific feedback vasodilator effectors remain uncertain. Although a number of mediators have been considered, including adenosine, nitric oxide (NO), ATP-sensitive potassium (K_ATP) channels, endothelium-derived hyperpolarizing factor (candidates include CO, H₂O₂, or ONOO^–), and prostacyclin,^2,4 the specific blockade of many of these pathways fails to completely inhibit hypoxic vasodilation.²

Article p 670

The present study published by Maher and colleagues⁵ in this issue of Circulation provides compelling evidence in normal human volunteers that the circulating anion salt nitrite (NO₂^–) may be an effector of hypoxic vasodilation. They report that . . . [Full Text of this Article]