Responsiveness And Density Of Non-Adrenergic Receptors In Skeletal Muscle Of Young And Old Beagles

Abstract

A tonic increase in muscle sympathetic nerve activity (MSNA) has been associated with advancing age. Whether this tonic increase in efferent sympathetic nerve activity alters non-adrenergic protein expression and the responsiveness of non-adrenergic receptors in resting and contracting skeletal muscles has not been clearly established. Therefore, the purpose of the present study was to investigate the effect of aging on the density and responsiveness of neuropeptide Y - Y1 (NPY) and purinergic (P2X) receptors in skeletal muscle. Young (n = 6; 22 ± 3) and old (n= 7; 119 ± 22 months) beagles were instrumented chronically with transit-time flow probes on the external iliac arteries and an indwelling catheter in a branch of the femoral artery. On separate days, flow-adjusted doses of selective NPY (Leu31-Pro34 NPY; 1 ug/ml/min) and P2X (a-b-methylene ATP; 1 ug/ml/min) agonists were infused at rest and during treadmill running at 2.5 miles/h and 4 miles/h with 2.5% grade. Hindlimb blood flow (HBF) and mean arterial pressure (MAP) were recorded continuously and vascular conductance (VC) was calculated as HBF/MAP. After dissecting feed arteries from gracillis muscles, NPY and P2X receptor protein content was determined by Western Blot and adjusted for b-actin content. Infusion of NPY resulted in similar (p > 0.05) declines in VC in young and old beagles at rest (Young: -40 ± 18 %; Old: -39 ± 23 %) and during exercise at 2.5 miles/h (Young: -47 ± 14 %; Old: -40 ± 15 %) and 4 miles/h with 2.5% grade (Young: -40 ± 8 %; Old: -38 ± 5 %). a-b-methylene ATP infusion also produced similar (p > 0.05) decreases in VC in young and old beagles at rest (Young: -36 ± 20 %; Old: -40 ± 10 %) and during exercise at 2.5 miles/h (Young: -42 ± 21 %; Old: -40 ± 23 %) and 4 miles/h with 2.5% grade (Young: -47 ± 12 %; Old: -42 ± 20 %). NPY and P2X receptor protein expression were similar (p > 0.05) in young and old beagles. These results demonstrate that the vascular response to selective NPY and P2X receptor agonists does not decline with advancing age. Moreover, the similar receptor protein expression suggests that the tonic increase in efferent MSNA with aging does not alter the density of post-synaptic receptors in canine feed arteries.