Neuropeptide Y1 receptor vasoconstriction in exercising canine skeletal muscles.
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 alpha-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 alpha-adrenergic receptor-mediated vasoconstriction.
Buckwalter
John B
JB
Department of Anesthesiology, Medical College of Wisconsin, Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. jbuckwal@mcw.edu
Hamann
Jason J
JJ
Clifford
Philip S
PS
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000502:physiology*; D004285:Dogs; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
C092926:BIBP 3226; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine