Mixed meal and light exercise each recruit muscle capillaries in healthy humans

Abstract

Intense exercise and insulin each increases total limb blood flow and recruits muscle capillaries, presumably to facilitate nutrient exchange. Whether mixed meals or light exercise likewise recruits capillaries is unknown. We fed 18 (9 M, 9 F) healthy volunteers a 480-kcal liquid mixed meal. Plasma glucose, insulin, brachial artery flow, and forearm muscle microvascular blood volume were measured before and after the meal. Brachial artery flow and microvascular volume were also examined with light (25% max), moderate (50%), and heavy (80%) forearm contraction every 20 s in 5 (4 M, 1 F) healthy adults. After the meal, glucose and insulin rose modestly (to ϳ7 mM and ϳ270 pM) and peaked by 30 min, whereas brachial artery blood flow (P Ͻ 0.05) and the microvascular volume (P Ͻ 0.01) each increased significantly by 60 min, and microvascular flow velocity did not change. For exercise, both 50 and 80%, but not 25% maximal handgrip, increased average forearm and brachial artery blood flow (P Ͻ 0.01). Flow increased immediately after each contraction and declined toward basal over 15 s. Exercise at 25% max increased microvascular volume threefold (P Ͻ 0.01) without affecting microvascular flow velocity or total forearm blood flow. Forearm exercise at 80% maximal grip increased both microvascular volume and microvascular flow velocity (P Ͻ 0.05 each). We conclude that light exercise and simple meals each markedly increases muscle microvascular volume, thereby expanding the endothelial surface for nutrient exchange, and that capillary recruitment is an important physiological response to facilitate nutrient/hormone delivery in healthy humans. INSULIN (1, 7, 18) AND EXERCISE (8, 13) each increase total limb blood flow, and each recruits flow to muscle capillaries (13,18). These vascular responses facilitate the delivery of oxygen, insulin, and glucose to muscle cells. Flow to individual capillary networks is controlled by small, ϳ20 m diameter terminal arterioles (21). We previously showed that during insulin infusion, relaxation of larger-resistance arterioles (which contribute to the regulation of total blood flow) and terminal arterioles can occur independently in rat (25, 29) and human (7) muscle.Muscle microvascular responses to physiological stimuli have been difficult to assess in humans due to the lack of noninvasive techniques suitable for assessing microvascular blood volume. We have developed two independent techniques for determining muscle microvascular volume noninvasively.The first technique is based on the metabolism of exogenously infused 1-methylxanthine (1-MX) to 1-methylurate by capillary endothelial xanthine oxidase (18,29). This has worked well in rodent models but has not been adapted to human studies. The second technique, contrast-enhanced ultrasound (CEU), relies on the contrast introduced by intravenously infused microbubbles (27). To measure microvascular volume, CEU takes advantage of the fact that during their continuous infusion it is possible to disrupt microbubbles by a single pulse of high...

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

“…Here we have again shown that age-related decrements in LBF are associated with impairments in muscle MBV responses to feeding, findings that are consistent with reports of decrements in fed-state forearm MBF (inferred from indirect measurements) (Skilton et al 2005) and also the absence of increased muscle MBF in older people fed EAA and sucrose (Timmerman et al 2012). Whereas it is well established that acute bouts of exercise enhance microvascular perfusion in both human (Vincent et al 2006) and rodent muscle (Sjøberg et al 2011), the effects of an acute neutraceutical intervention (in this case cocoa flavanols) on muscle MBF in response to nutrition, have until now remained poorly defined. Here, we have shown that 350 mg cocoa flavanols improved nutrient-dependent increases in both LBF and muscle MBF in older men.…”

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

“…The hypothesis that insulin recruits capillaries in muscle to facilitate its own delivery to target tissues by increasing the available endothelial surface has been examined using a variety of methods including laser Doppler (25), 1-methyl xanthinine metabolism (29,30), and CEU (12)(13)(14)(15)(16)31). At physiological doses, the effect of insulin to increase microvascular perfusion occurs earlier than changes in total flow or glucose uptake (14,16).…”

“…In humans, physiological hyperinsulinemia increases microvascular recruitment by 120 min (16,31). However, the early time course of microvascular recruitment has not been defined.…”

Contrast-enhanced ultrasound measurement of microvascular perfusion relevant to nutrient and hormone delivery in skeletal muscle: A model study in vitro

“…There are four studies, three involving human forearm Coggins et al, 2001;Vincent et al, 2006) and one on rat hindlimb muscle (Dawson et al, 2002) in which CEU/ microbubbles have been used in vivo to determine changes in capillary recruitment. For the rat, the stimuli that gave rise to capillary recruitment were muscle contraction and insulin.…”

“…These studies can not be conducted in vivo and only one previous modeling study of this kind has been reported (Wei et al, 1998) where bulk flow was shown to correlate well with measured filling rate, but capillary volume was not determined. Accordingly, in the present study, CEU is used with constructed capillary tubing models in vitro to assess the effect of bulk flow and its potential for discriminating between different flow patterns within muscle that might explain capillary recruitment reported in vivo (Dawson et al, 2002;Rattigan et al, 1997;Vincent et al, 2006).…”