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J Appl Physiol (May 23, 2003). doi:10.1152/japplphysiol.00173.2003
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Submitted on February 19, 2003
Accepted on May 19, 2003

Vasoconstriction in Active Skeletal Muscles: A Potential Role for P2X Purinergic Receptors?

John B Buckwalter1*, Jason J Hamann1, and Philip S Clifford1

1 Departments of Anethesiology and Physiology, Medical College of Wisconsin and VA Medical Center, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: jbuckwal{at}mcw.edu.

There is evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is co-released with norepinephrine from sympathetic nerves. We hypothesized that P2X receptor stimulation with the selective P2X receptor agonist, {alpha},{beta}-methylene ATP would produce vasoconstriction in resting and exercising skeletal muscle. Six mongrel dogs were instrumented chronically with flowprobes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective P2X agonist, {alpha},{beta}-methylene ATP was infused as a bolus into the femoral artery catheter at rest and during mild, moderate and heavy exercise. Intraarterial infusions of {alpha},{beta}-methylene ATP elicited reductions in vascular conductance of 54±5, 49±8, 39±8 and 30±6 % at rest, 3 miles/h, 6 miles/h and 6 miles/h at a 10% grade, respectively. The agonist infusions did not affect blood flow in the contralateral iliac artery. To examine whether nitric oxide is responsible for the attenuated vasoconstrictor response to P2X stimulation, the infusions were repeated in the presence of L-NAME. After nitric oxide synthase blockade, intraarterial infusions of {alpha},{beta}-methylene ATP elicited reductions in vascular conductance of 56±7, 61±8, 52±9 and 40±7 % at rest, 3 miles/h, 6 miles/h and 6 miles/h at a 10% grade, respectively. P2X receptor responsiveness was attenuated during exercise compared to rest. Blockade of nitric oxide production did not effect the attenuation of P2X receptor responsiveness during exercise. These data support the hypothesis that P2X purinergic receptors can produce vasoconstriction in exercising skeletal muscle.




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