title: Erythrocytes as controllers of perfusion distribution in the microvasculature of skeletal muscle.
abstract: In 1929, August Krogh identified the matching of oxygen (O(2)) supply with demand in skeletal muscle as a fundamental physiological process. In the intervening decades, much research has been focused on elucidating the mechanisms by which this important process occurs. For any control system to be effective, there must be a means by which the need is determined and a mechanism by which that information is coupled to an appropriate response. The focus of this review was to highlight current research in support of the hypothesis that the mobile erythrocyte, when exposed to reduced O(2) tension, releases ATP in a controlled manner. This ATP interacts with purinergic receptors on the endothelium producing both local and conducted vasodilation enabling the erythrocyte to distribute perfusion to precisely match O(2) delivery with need in skeletal muscle. If this is an important mechanism for normal physiological control of microvascular perfusion, defects in this process would be anticipated to have pathophysiological consequences. Individuals with either type 2 diabetes (DM2) or pre-diabetes have microvascular dysfunction that contributes to morbidity and mortality. DM2 erythrocytes and erythrocytes incubated with insulin at levels similar to those seen in pre-diabetes fail to release ATP in response to reduced O(2) tension. Knowledge of the components of the signal transduction pathway for low O(2) -induced ATP release suggest novel therapeutic approaches to ameliorating this defect. Although the erythrocyte may be but one component of the complex O(2) delivery process, it appears to play an important role in distributing oxygen within the microvasculature.
authors: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. spraguer@slu.edu
authors: R S
authors: RS
authors: Sprague
authors: E A
authors: EA
authors: Bowles
authors: D
authors: D
authors: Achilleus
authors: M L
authors: ML
authors: Ellsworth
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000077407:Cilostazol; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D055806:Microvessels / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D010100:Oxygen / Q000097:blood*; D010455:Peptides / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D010455:Peptides; D013777:Tetrazoles; D014665:Vasodilator Agents; D002110:Caffeine; D000255:Adenosine Triphosphate; D000077407:Cilostazol; D010100:Oxygen