The effect of aging on adrenergic and nonadrenergic receptor expression and responsiveness in canine skeletal muscle

Abstract

We tested the hypothesis that adrenergic and nonadrenergic receptor responsiveness and protein expression would be altered with advancing age. Young ( n = 6; 22 ± 1 mo; mean ± SE) and old ( n = 6; 118 ± 9 mo) beagles were instrumented with flow probes and an indwelling catheter for continuous measurement of external iliac blood flow and arterial blood pressure. Vascular conductance (VC) was calculated as hindlimb blood flow/mean arterial pressure. Selective agonists for α-1, α-2, neuropeptide-Y (NPY), and purinergic (P2X) receptors were infused at rest and during treadmill running at moderate (2.5 mph) and heavy (4 mph with 2.5% grade) exercise intensities. Feed arteries were dissected from gracilis muscles, and α-1D, α-1B, α-2A, P2X-4, P2X-1, and NPY-Y1 receptor protein expression was determined. Phenylephrine produced similar decreases ( P > 0.05) in VC in young and old beagles at rest (young: −62 ± 5%; old: −59 ± 5%) and during moderate (young: −67 ± 5%; old: −62 ± 4%) and heavy (young: −54 ± 4%; old: −49 ± 3%) exercise. Clonidine caused similar ( P > 0.05) decreases in VC in old compared with young dogs at rest (young: −59 ± 8%; old: −70 ± 6%) and during moderate (young: −52 ± 6%; old: −47 ± 5%)- and heavy (young: −42 ± 5%; old: −43 ± 5%)-intensity exercise. NPY infusion resulted in a similar decline in VC in young and old beagles at rest (young: −40 ± 7%; old: −39 ± 9%) and during moderate (young: −47 ± 6%; old: −40 ± 6%)- and heavy (young: −40 ± 3%; old: −38 ± 4%)-intensity exercise. α-β-Methylene-ATP also produced similar decreases in VC in young and old beagles at rest (young: −36 ± 6%; old: −40 ± 8%) and during exercise at moderate (young: −42 ± 5%; old: −40 ± 9%) and heavy (young: −47 ± 5%; old: −42 ± 8%) intensities. α-1B receptor protein expression was elevated ( P < 0.05) in old compared with young dogs, whereas there were no age-related differences in α-1D or α-2A receptor expression and nonadrenergic P2X-4, P2X-1, and NPY-Y1 receptor expression. The present findings indicate that postsynaptic adrenergic and nonadrenergic receptor responsiveness was not altered by advancing age. Moreover, the expression of adrenergic and nonadrenergic receptors in skeletal-muscle feed arteries was largely unaffected by aging.