Neuropeptide Y1 receptor vasoconstriction in exercising canine skeletal muscles

Departments of Anesthesiology and Physiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, Wisconsin Submitted 15 April 2005 ; accepted in final form 8 August 2005 Existing evidence suggests that neuropeptide Y (NPY) acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves. We hypothesized that release of NPY stimulates NPY Y 1 receptors in the skeletal muscle vasculature to produce vasoconstriction during dynamic exercise. Eleven mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. In resting dogs ( n = 4), a 2.5-mg bolus of BIBP-3226 (NPY Y 1 antagonist) infused into the femoral artery increased external iliac conductance by 150 ± 82% (1.80 ± 0.44 to 3.50 ± 0.14 ml·min –1 ·mmHg –1 ; P < 0.05). A 10-mg bolus of BIBP-3226 infused into the femoral artery in dogs ( n = 7) exercising on a treadmill at a moderate intensity (6 miles/h) increased external iliac conductance by 28 ± 6% (6.00 ± 0.49 to 7.64 ± 0.61 ml·min –1 ·mmHg –1 ; P < 0.05), whereas the solvent vehicle did not (5.74 ± 0.51 to 5.98 ± 0.43 ml·min –1 ·mmHg –1 ; P > 0.05). During exercise, BIBP-3226 abolished the reduction in conductance produced by infusions of the NPY Y 1 agonist [Leu 31 ,Pro 34 ]NPY (–19 ± 3 vs. 0.5 ± 1%). Infusions of BIBP-3226 ( n = 7) after -adrenergic receptor antagonism with prazosin and rauwolscine also increased external iliac conductance (6.82 ± 0.43 to 8.22 ± 0.48 ml·min –1 ·mmHg –1 ; P < 0.05). These data support the hypothesis that NPY Y 1 receptors produce vasoconstriction in exercising skeletal muscle. Furthermore, the NPY Y 1 receptor-mediated tone appears to be independent of -adrenergic receptor-mediated vasoconstriction. blood flow; sympathetic nervous system; autonomic nervous system Address for reprint requests and other correspondence: J. Buckwalter, Anesthesia Research 151, VA Medical Center, 5000 W. National Ave., Milwaukee, WI 53295 (e-mail: jbuckwal{at}mcw.edu )