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(Circulation Research. 2003;92:821.)
© 2003 American Heart Association, Inc.

Editorials

Surviving Hypoxia

The Importance of Rafts, Anchors, and Fluidity

Aruni Bhatnagar

From the Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Ky.

Correspondence to Aruni Bhatnagar, PhD, Division of Cardiology, Department of Medicine, Jewish Cardiovascular Research Center, 500 South Floyd St, University of Louisville, Louisville, KY 40202. E-mail aruni@louisville.edu

Key Words: hypoxia • adenosine • ecto-5'-nucleotidase • membrane fluidity • endothelium

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

Oxidative phosphorylation is the major energy-generating mechanism in aerobic cells. Although most cells can temporarily subsist on glycolysis, continued supply of oxygen is critical for maintaining high levels of mechanical, electrical, and metabolic activity. As a result, a wide range of biological responses of varying complexity have evolved to adapt to hypoxia and to optimize oxygen utilization. Currently, these responses are poorly understood. However, extant data provide a tantalizing glimpse into the rich diversity of these responses that range from the stimulation of signaling cascades and gene transcription events to the changes in excitability and blood flow.

Optimal function during hypoxia could be preserved either by reducing oxygen consumption or by optimizing oxygen delivery. Both these responses are triggered in hypoxic tissues and are mediated in part by adenosine. When oxygen is plentiful, adenosine is in the cells in the form of either ATP or ADP. However, during hypoxia, most cells release nucleotides into the extracellular space where the nucleotides are cleaved to adenosine by ecto-5'-nucleotidase (E5'N, CD73¹). Interstitial adenosine is either internalized (for nucleotide salvage) or it binds to one of its receptors (A₁, A_2A, A_2B and A₃) on the cell surface to induce a variety of tissue- and receptor-specific responses. Adenosine-initiated signaling pathways are generally protective and mitigate against the harmful effects of hypoxia.² During systemic hypoxia, for instance, adenosine plays an essential role in causing dilation of arterioles, which helps in maintaining oxygen delivery³; and in the heart, adenosine-mediated signaling triggers early . . . [Full Text of this Article]

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