Arteriolar network architecture and vasomotor function with ageing in mouse gluteus maximus muscle

Abstract

Physical diminishes with ageing, but little is known of how the microvascular supply to skeletal muscle fibres is affected. To test the hypothesis that ageing alters blood flow control, we investigated network architecture and vasomotor responses of arterioles in the gluteus maximus muscle of young (2-3 months), adult (12-14 months) and old (18-20 months) C57BL6 male mice (n = 83) (Young, Adult and Old, respectively). Microvascular casts revealed that the total number, length and surface area of arteriolar segments (diameter, 10-50 µm) were not significantly different across age-groups. However, for arterioles with diameter of 30 µm, tortuosity and branch angles increased with age (P < 0.05). In anaesthetized mice, second-order (2A) distributing arterioles had similar resting (17 ± 1 µm) and maximal (37 ± 1 µm) diameters and similar responsiveness to cumulative (10 −10 −10 −4 M) superfusion of acetylcholine or phenylephrine. With superfusate oxygen level raised from 0 to 21%, 2A arteriolar constriction in Young (11 ± 1 µm) was greater (P < 0.05) than Adult and Old (5 ± 1 µm). Observed 1 mm upstream from microiontophoresis of ACh (1 µA, 1 s), conducted vasodilatation was 10 ± 1 µm in Young, 17 ± 1 µm in Adult and 6 ± 1 µm in Old (P < 0.05). With muscle contractions (2, 4 and 8 Hz; 30 s) arteriolar diameter increased similarly across age-groups (6 ± 1, 11 ± 1 and 18 ± 1 µm, respectively). Muscle mass and active tension were similar across age-groups yet postcontraction vasodilatation recovered more rapidly in Old versus Adult and Young (P < 0.05). With arteriolar network architecture maintained during ageing, the impairment in conducted vasodilatation and attenuation of postcontraction vasodilatation may compromise exercise tolerance.

Advancing age produces sex differences in vasomotor kinetics during and after skeletal muscle contraction

“…In our study, the steady-state diameters at baseline and during contractions were not different across groups, suggesting that the demand for blood flow was not different. This is consistent with our previous findings that age does not impair force production or the work done during contractions by this muscle (8). Findings in humans have demonstrated that differences in muscle fatigability between the sexes (males more fatigable than females) may depend on blood flow control because ischemia abolishes the difference (35).…”

“…The gluteus maximus is primarily a fast-twitch muscle (24,25) and is used in voluntary locomotion (8). We have also reported that the topology of the microvascular network is genetically determined and does not change throughout life (7,8). For these reasons, we are able to study the "same" vessel (same branch and vessel segment within the microvascular network) in every animal.…”

“…The muscle is parallel fibered, with fibers running from the iliac crest and lumbar spine to the femur (gluteal tuberosity) and iliotibial band. The gluteus maximus is primarily a fast-twitch muscle (24,25) and is used in voluntary locomotion (8). We have also reported that the topology of the microvascular network is genetically determined and does not change throughout life (7,8).…”

“…Mice were anesthetized with pentobarbital (75 mg/kg body mass ip). For intravital microscopy, a gluteus maximus muscle was exposed by removing the overlying skin and connective tissue, cut free from its proximal attachment, reflected away from the body, and positioned on a clear Sylgard pedestal at in vivo length (8) and was allowed to superfuse the preparation for 45-60 min before further measurements. The optical image was coupled to a chargecoupled device video camera through a ϫ20 objective on a Leica DMLFS microscope and was displayed on a closed-circuit television video monitor (Tatung) to a final magnification of ϫ1670.…”

Age-related changes in conducted vasodilation: effects of exercise training and role in functional hyperemia

“…Moreover, the mechanistic requirement of conducted vasodilation has not been investigated under physiological conditions, where the capacity for conducted vasodilation changes naturally rather than through experimental manipulation. We recently reported that the capacity to conduct vasodilation is age dependent (4), providing a novel model for studying the role of conducted vasodilation in skeletal muscle blood flow regulation. The purpose of this study was to test the hypotheses that 1) exercise training would enhance conducted vasodilation along arterioles of the gluteus maximus muscle and 2) that age-related changes in conducted vasodilation are reflected in concomitant changes in functional hyperemia.…”