Responsiveness and density of alpha‐adrenergic receptors in skeletal muscle of young and old beagles

Abstract

Whether the tonic increase in muscle sympathetic nerve activity that has been associated with aging alters α‐adrenergic receptor protein expression and responsiveness has not been established. The purpose was to investigate the effect of aging on the density and responsiveness of α1‐ and α2–adrenergic–receptors in skeletal muscle. Young (n = 6; 22 ± 3 mo.) and old (n= 7; 119 ± 22 mo.) beagles were instrumented with flow probes on the external iliacs and a catheter in a branch of the femoral artery. Flow‐adjusted doses of selective α1‐ (phenylephrine (PE); 0.05 ug/ml/min) and α2–adrenergic‐receptor (clonidine; 0.1 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 and vascular conductance (VC) was calculated. Gracillis muscle feed arteries were dissected and receptor protein content was determined by Western Blot. PE infusion resulted in a similar decline in VC in young and old at rest (Young: −59 ± 11 %; Old: −62 ± 13 %) at 2.5 miles/h (Young: −62 ± 10 %; Old: −67 ± 13 %) and 4 miles/h with 2.5% grade (Young: −49 ± 8 %; Old: −54 ± 9 %). Clonidine infusion also produced similar decreases in VC in young and old at rest (Young: −70 ± 14 %; Old: −59 ± 19 %) at 2.5 miles/h (Young: −47 ± 13 %; Old: −52 ± 15 %) and 4 miles/h with 2.5% grade (Young: −43 ± 13 %; Old: −43 ± 12 %). α1D and α2A receptor protein expression was similar, whereas α1B receptor protein expression was 17% greater (p<0.05) in old compared to young. The vascular response to α1‐ and α2–adrenergic‐receptor agonists does not decline with aging. The similar vascular response to PE suggests that the age‐related decline in α1B receptor expression was offset by an increase in receptor responsiveness.