Impact of age on the vasodilatory function of human skeletal muscle feed arteries

Abstract

Although advancing age is often associated with attenuated skeletal muscle blood flow and skeletal muscle feed arteries (SMFAs) have been recognized to play a regulatory role in the vasculature, little is known about the impact of age on the vasodilatory capacity of human SMFAs. Therefore, endothelium-dependent and -independent vasodilation were assessed in SMFAs (diameter: 544 ± 63 μm) obtained from 24 (equally represented) young (33 ± 2 yr) and old (71 ± 2 yr) subjects in response to three stimuli: 1) flow-induced shear stress, 2) ACh, and 3) sodium nitropusside (SNP). Both assessments of endothelium-dependent vasodilation, flow (young subjects: 68 ± 1% and old subjects: 32 ± 7%) and ACh (young subjects: 92 ± 3% and old subjects: 73 ± 4%), were significantly blunted (P < 0.05) in SMFAs of old compared with young subjects, with no such age-related differences in endothelium-independent vasodilation (SNP). In response to an increase in flow-induced shear stress, vasodilation kinetics (time constant to reach 63% of the amplitude of the response: 55 ± 1 s in young subjects and 92 ± 7 s in old subjects) and endothelial nitric oxide synthase (eNOS) activation (phospho-eNOS(s1177)/total eNOS: 1.0 ± 0.1 in young subjects and 0.2 ± 0.1 in old subjects) were also significantly attenuated in old compared with young subjects (P < 0.05). Furthermore, the vessel superoxide concentration was greater in old subjects (old subjects: 3.9 ± 1.0 area under curve/mg and young subjects: 1.7 ± 0.1 area under the curve/mg, P < 0.05). These findings reveal that the endothelium-dependent vasodilatory capacity, including vasodilation kinetics but not smooth muscle function, of human SMFAs is blunted with age and may be due to free radicals. Given the potential regulatory role of SMFAs in skeletal muscle blood flow, these findings may explain, at least in part, the often observed attenuated perfusion of skeletal muscle with advancing age that may contribute to exercise intolerance in the elderly.

Keywords: aging; endothelium-dependent vasodilation; human skeletal muscle feed artery.

Figures

Fig. 1.

Skeletal muscle feed artery (SMFA) peak percentage of vasodilation induced by flow, ACh, and sodium nitropruside (SNP) in young and old subjects. Data are expressed as means ± SE; n = 12 young and 12 old subjects. *Significantly different from young subjects, P < 0.05.

Fig. 2.

SMFA vasodilatation kinetics illustrated as absolute changes in diameter (A) and percentages of vasodilation (B) in young and old subjects. Data are expressed as means ± SE; n = 12 young and 12 old subjects. *Significant difference between young and old subjects, P < 0.05.

Fig. 3.

SMFA vasodilation kinetics in response to flow (A) and increasing doses of ACh (B) in the absence or presence of the nitric oxide synthase (NOS) inhibitor N-monomethyl-l-arginine (l-NMMA) in young and old subjects. n = 6 young and 6 old subjects. *Significant difference between young and old subjects, P < 0.05; †Significant difference between flow alone and with l-NMMA, P < 0.05.

Fig. 4.

SMFA endothelium-dependent vasodilation induced by increasing doses of ACh (A) and endothelium-independent vasodilation induced by increasing doses of SNP (B) in young and old subjects. Data are expressed as means ± SE; n = 12 young and 12 old subjects. *Significant difference between young and old subjects, P < 0.05.

Fig. 5.

Total endothelial NOS (eNOS) and phosphorylated (p-)eNOS at Ser1177 in SMFAs of young (y) and old (o) subjects under basal conditions (A) and changes induced by 6 min of flow inducing a shear rate of ∼500 s−1 (B). Data are expressed as means ± SE; n = 8 young and 8 old subjects. *Significantly different from young subjects, P < 0.05.

Fig. 6.

Basal superoxide level, as assessed by 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine adduct, in young and old SMFAs assessed by electron paramagnetic resonance (EPR) spectroscopy. The EPR signal is expressed as the area under the curve (AUC; in arbitrary units). Representative spectroscopy signals are inlayed. Data are expressed as means ± SE; n = 8 young and 8 old subjects. *Significantly different from young subjects, P < 0.05.