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

Departments of Anesthesiology and Physiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 Submitted 28 January 2004 ; accepted in final form 22 February 2004 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 Y 1 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 Y 1 receptor agonist [Leu 31 ,Pro 34 ]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 ,Pro 34 ]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 Y 1 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 Y 1 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 Y 1 receptor responsiveness during exercise. These data support the hypothesis that NPY Y 1 receptors can produce vasoconstriction in exercising skeletal muscle. blood flow; sympatholysis; autonomic nervous system; dogs Address for reprint requests and other correspondence: J. B. Buckwalter, Anesthesia Research 151, VA Medical Center, Milwaukee, WI 53295 (E-mail: jbuckwal{at}mcw.edu ).