TY - JOUR
T1 - Vasoconstriction in active skeletal muscles
T2 - A potential role for P2X purinergic receptors?
AU - Buckwalter, John B.
AU - Hamann, Jason J.
AU - Clifford, Philip S.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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 α,β-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 α,β-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 α,β-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, intraarterial infusions of α,β-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.
AB - 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 α,β-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 α,β-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 α,β-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, intraarterial infusions of α,β-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.
KW - Autonomic nervous system
KW - Blood flow
KW - Dogs
KW - Sympatholysis
UR - http://www.scopus.com/inward/record.url?scp=0042423597&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.00173.2003
DO - 10.1152/japplphysiol.00173.2003
M3 - Article
C2 - 12766177
AN - SCOPUS:0042423597
SN - 8750-7587
VL - 95
SP - 953
EP - 959
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 3
ER -