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

Abstract

Bearden SE, Linn E, Ashley BS, Looft-Wilson RC. Age-related changes in conducted vasodilation: effects of exercise training and role in functional hyperemia. Am J Physiol Regul Integr Comp Physiol 293: R1717-R1721, 2007. First published July 25, 2007; doi:10.1152/ajpregu.00827.2006.-Conducted vasodilation may coordinate blood flow in microvascular networks during skeletal muscle contraction. We tested the hypotheses that 1) exercise training enhances conducted vasodilation and 2) age-related changes in the capacity for conduction affect muscle perfusion during contractions. To address hypothesis 1, young (4 -5 mo), adult (12-14 mo), and old (19 -21 mo) C57BL6 male mice were sedentary or given access to running wheels for 8 wk. Voluntary running distances were significantly different (in km/day): young ϭ 5.8 Ϯ 0.1, adult ϭ 3.9 Ϯ 0.1, old ϭ 2.2 Ϯ 0.1 (P Ͻ 0.05). In gluteus maximus muscles, conducted vasodilation was greater in adult than in young or old mice (P Ͻ 0.05) and greater in young sedentary than in old sedentary mice but was not affected by exercise training. Citrate synthase activity was greater with exercise training at all ages (P Ͻ 0.05). mRNA for endothelial nitric oxide synthase did not differ among ages, but endothelial nitric oxide synthase protein expression was greater in adult and old mice with exercise training (P Ͻ 0.05). Connexin 37, connexin 40, and connexin 43 mRNA were not affected by exercise training and did not differ by age. To address hypothesis 2, perfusion of the gluteus maximus muscle during light to severe workloads was assessed by Doppler microprobe at 3-26 mo of age. Maximum perfusion decreased linearly across the lifespan. Perfusion at the highest workload, absolute and relative to maximum, decreased across the lifespan, with a steeper decline beyond ϳ20 mo of age. In this model, 1) exercise training does not alter conducted vasodilation and 2) muscle perfusion is maintained up to near maximum workloads despite age-related changes in conducted vasodilation. endothelial; smooth muscle; gap junction; microcirculation; aging THE CAPACITY TO COORDINATE vasodilation among branches of a microvascular network, especially between distal and proximal branches, may contribute to the regulation of blood flow control in contracting skeletal muscle (22,23). Conducted vasodilation is one mechanism hypothesized to mediate coordinated vasodilation. For example, destruction of the endothelial cell monolayer in feed arteries to the hamster retractor muscle, thereby blocking conducted vasodilation, reduces blood flow through this vessel consequent to muscle contraction (23). Whether conducted vasodilation is required for muscle perfusion during contraction of locomotor muscle or whether it is modified by exercise training remains unknown. 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 ...

Late cardioprotection of exercise preconditioning against exhaustive exercise-induced myocardial injury by up-regulatation of connexin 43 expression in rat hearts

“…The RT-PCR results showed that no significant differences in the Cx43 mRNA levels were found between the groups, as supported by the in situ hybridization detection. Obvious decreased expression of Cx43 mRNA was found in trained mice during acute exercise [20,35] , while chronic exercise training has no effect on the expression of Cx43 mRNA in intact blood vessels in vivo [36] . Therefore, we speculated that different exercise intensity has different effects on the expression of Cx43 mRNA.…”

Connexin40 Imparts Conduction Heterogeneity to Atrial Tissue

“…Although Western blot and immunohistological analysis did not demonstrate significant right–left differences in Cx40 protein expression in the Cx40 +/+ mice, quantification of Cx40 mRNA expression found chamber-specific differences that followed a similar pattern to the CV findings. It is recognized that qRT-PCR is an assay that is less variable than Western blot 28. Heterogeneity in Cx40 mRNA expression (LAA>RAA) was detected in Cx40 +/+ mice and lost with partial deletion of Cx40, mirroring CV findings.…”

Age-related impairment of conducted dilation in human coronary arterioles

“…To furnish evidence for this scenario our functional experiments show that after the SK Ca /IK Ca channels (known mediators of EDHF and hyperpolarization spread) (2) were inhibited or in the presence of 30 mM K ϩ solution (known to inhibit EDHF response), the conducted coronary dilation to bradykinin is abolished. Given that previous studies found an impaired conducted vasodilation in the skeletal muscle of rodent models of aging (1,2), in this study we also determined whether the conducted dilation is altered in coronary resistance arteries of older patients. We found a significant reduction in conducted dilation to bradykinin in older (Ն64 yr) patients compared with younger individuals (Ͻ64 yr).…”

“…Behringer et al (2) have shown that aging impairs electrical conduction along endothelial cell tubes obtained from resistance arteries of the 24-to 26-mo-old mice. In old (19 to 20 mo) mice, Bearden et al (1) found that conducted vasodilation is reduced in the skeletal muscle microcirculation, in vivo, compared with younger (12-14 mo) mice. These data indicate that aging impairs conducted vasodilation in the skeletal muscle circulation and demonstrate a key role in dysfunctional microvascular endothelium in this process.…”