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Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise?

Departments of Anesthesiology and Physiology, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295

Submitted 18 June 2003 ; accepted in final form 5 October 2003

Although there is evidence that sympathetic nerves release ATP as a neurotransmitter to produce vasoconstriction via P2X purinergic receptors, the role of these receptors in the regulation of blood flow to exercising skeletal muscle has yet to be determined. We hypothesized that there is tonic P2X receptor-mediated vasoconstriction in exercising skeletal muscle. To test this hypothesis, the effect of P2X receptor blockade on skeletal muscle blood flow was examined in six exercising mongrel dogs. P2X receptor antagonism was accomplished with pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid (PPADs). Animals were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. PPADs (40 mg) was infused as a bolus into the femoral artery catheter during steady-state exercise at 6 miles/h. Intra-arterial infusion of PPADs increased iliac blood flow from 542 ± 55 to 677 ± 69 ml/min (P < 0.05) and iliac vascular conductance from 5.17 ± 0.62 to 6.53 ± 0.80 ml·min^–1·mmHg^–1. The PPADs infusion did not affect blood flow in the contralateral iliac artery. These data support the hypothesis that P2X purinergic receptors produce vasoconstriction in exercising skeletal muscle.

ATP; sympathetic nervous system; dogs; blood pressure; vasomotor tone

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