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

Abstract

Little is known of the vasomotor responses of skeletal muscle arterioles during and following muscle contraction. We hypothesized that aging leads to impaired arteriolar responses to muscle contraction and recovery. Nitric oxide (NO) availability, which is age dependent, has been implicated in components of these kinetics. Therefore, we also hypothesized that changes in the kinetics of vascular responses are associated with the NO pathway. Groups were young (3 mo), old (24 mo), endothelial NO synthase knockout (eNOS−/−), and NG-nitro-l-arginine (l-NA)-treated male and female C57BL/6 mice. The kinetics of vasodilation during and following 1 min of contractions of the gluteus maximus muscle were recorded in second-order (regional distribution) and third-order (local control) arterioles. Baseline, peak (during contraction), and maximal diameters (pharmacological) were not affected by age or sex. The kinetics of dilation and recovery were not different between males and females at the young age. There was a significant slowing of vasodilation at the onset of contractions (∼2-fold; P < 0.05) and a significant speeding of recovery (∼5-fold; P < 0.05) in old males vs. old females and vs. young eNOS−/−, and l-NA did not affect the kinetics at the onset of muscle contraction. eNOS−/− mimicked the rapid recovery of old males in second-order arterioles; acute NO production (l-NA) explained ∼50% of this effect. These data demonstrate fundamental age-related differences between the sexes in the dynamic function of skeletal muscle arterioles. Understanding how youthful function persists in females but not males may provide therapeutic insight into clinical interventions to maintain dynamic microvascular control of nutrient supply with age.

Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization

“…As discussed previously, HFrEF and exercise training induce a profound redistribution of Q m among and within the limb musculature even in the face of unchanged bulk Q m (137,203,228). These adaptations reflect considerable heterogeneities in vasomotor control along and across discrete vascular branches related to muscle fiber type, oxidative capacity, and arteriolar branch order (182, 186 -188, 202, 262, 302, 306, 311, 332) that may be susceptible to changes with age, disease, and training (13,26,29,31,137,220,224,228,276,284,292,303). Heterogeneities in vasomotor control are expected to contribute to the temporal dissociation between conduit artery and microvascular Q m responses to submaximal exercise (120) and thus complicate extrapolation of data along the vascular tree.…”

The effects of short recovery duration on VO2 and muscle deoxygenation during intermittent exercise

“…There is some controversy as to the time course of vasodilation to exercise [4 s (Bearden 2007;Gorczynski et al 1978) to [20 s (Gorczynski et al 1978)]. Changes may follow a two phase pattern with a rapid initial response (\5 s) and a delayed second phase ([20 s) (Rogers et al 2006).…”

The impact of vasoactive and inflammatory reagents on arteriolar vasomotion in the gluteus maximus of mice.

“…A slower rate of vasodilation in gluteus maximus 2A arterioles has already been observed in male mice when compared to females (Bearden, 2007), suggesting similar vasomotive reactions in the microcirculation. The greater function of circulation in the skeletal muscle of females needs further clarification.…”

“…Solutions are brought to neutral pH with the necessary salts to maintain physiological activity within the microvasculature. In addition, a constant bubbling of CO2/ N2 into all flowing solution will act as a buffer, maintaining pH at 7.38-7.44 (Bearden, 2007). Finally, all solutions are also immersed in a water bath calibrated to body temperature.…”

“…This NO donor directly relaxes arteriolar smooth muscle, thus allowing measurement of maximal diameter through vasodilatation (Brooks et al, 2008). Thus, baseline and maximal diameters provide an index of vasomotor tone during each experiment (Bearden, 2007). Also, having a tone value will describe the arteriole's reactivity when exposed to each reagent.…”