Vasoconstriction in exercising skeletal muscles: A potential role for neuropeptide Y?

There is evidence that neuropeptide Y (NPY) acts as a neurotransmitter in vascular smooth muscle and is released with norepinephrine from sympathetic nerves. We hypothesized that NPY Y₁ receptor stimulation would produce vasoconstriction in resting and exercising skeletal muscle. Nine 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 NPY Y₁ receptor agonist [Leu³¹,Pro³⁴]NPY was infused as a bolus into the femoral artery catheter at rest and during mild, moderate, and heavy exercise. Intra-arterial infusions of [Leu ³¹,Pro³⁴]NPY elicited reductions (P < 0.05) in vascular conductance of 38 ± 3, 25 ± 2, 17 ± 1, and 11 ± 1% at rest, 3 miles/h, 6 miles/h, and 6 miles/h and 10% grade, respectively. The agonist infusions did not affect (P > 0.05) blood flow in the contralateral iliac artery. To examine whether nitric oxide (NO) is responsible for the attenuated vasoconstrictor response during exercise to NPY Y₁ receptor stimulation, the infusions were repeated after NO synthase blockade. These infusions yielded reductions (P < 0.05) in vascular conductance of 47 ± 3, 23 ± 2, 19 ± 3, and 12 ± 2% at rest, 3 miles/h, 6 miles/h, and 6 miles/h and 10% grade, respectively. NPY Y₁ receptor responsiveness was attenuated (P < 0.05) during exercise compared with rest. Blockade of NO production did not affect (P > 0.05) the attenuation of NPY Y₁ receptor responsiveness during exercise. These data support the hypothesis that NPY Y₁ receptors can produce vasoconstriction in exercising skeletal muscle.