Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?
There is evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased 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 flow probes 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. Intra-arterial 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 NG-nitro-l-arginine methyl ester. After nitric oxide synthase blockade, intra-arterial 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 with rest. Blockade of nitric oxide production did not affect the attenuation of P2X-receptor responsiveness during exercise. These data support the hypothesis that P2X purinergic receptors can produce vasoconstriction in exercising skeletal muscle.
Buckwalter
John B
JB
Department of Anesthesiology and Physiology, Medical College of Wisconsin, Milwaukee, WI 53295, USA. jbuckwal@mcw.edu
Hamann
Jason J
JJ
Clifford
Philip S
PS
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine