Acute Lower Leg Heating Increases Exercise Capacity in Patients With Peripheral Artery Disease.

BACKGROUND/OBJECTIVE: In this pilot study, we tested the hypothesis that acute lower leg heating (LLH) increases postheating popliteal artery blood flow and 6-minute walk distance in patients with peripheral artery disease (PAD). METHODS: Six patients (5 male, 1 female) with PAD (69 ± 6.9 years; claudication: ankle-brachial index < 0.90) participated in 3 randomized treatment sessions (2-7 days apart): control or bilateral LLH conducted via water bath immersion (42°C; ~40-cm depth) for either 15 or 45 minutes. Popliteal artery blood flow (Doppler ultrasound) and arterial pressure were measured before and after LLH. Six-minute walk distance was measured on the control day and each experimental day 35 minutes post-LLH. RESULTS: Popliteal artery blood flow increased after heating in a duration-dependent manner (P < .05, postheating vs control for both heating conditions and between them). Six-minute walk distance increased by 10% and 12% after 15- and 45-minute heating treatments, respectively (P < .05 vs control session). CONCLUSIONS: Lower leg heating, for as short as 15 minutes, increases postheating leg perfusion and exercise capacity in patients with PAD.

Characterisation of regional skin temperatures in recreational surfers wearing a 2-mm wetsuit.

The purpose of this study was to investigate skin temperatures across surfers' bodies while wearing a wetsuit during recreational surfing. Forty-six male recreational surfers participated in this study. Participants were instrumented with eight wireless iButton thermal sensors for the measurement of skin temperature, a Polar RCX5 heart rate monitor and a 2-mm full wetsuit. Following instrumentation, participants were instructed to engage in recreational surfing activities as normal. Significant differences (p < 0.001) in skin temperature (Tsk) were found across the body while wearing a wetsuit during recreational surfing. In addition, regional skin temperature changed across the session for several regions of the body (p < 0.001), and the magnitude of these changes varied significantly between regions. We show for the first time that significant differences exist in skin temperature across the body while wearing a wetsuit during a typical recreational surfing session. These findings may have implications for future wetsuit design. Practitioner Summary: This study investigated the impact of wearing a wetsuit during recreational surfing on regional skin temperatures. Results from this study suggest that skin temperatures differ significantly across the body while wearing a 2-mm wetsuit during recreational surfing. These findings may have implications for future wetsuit design.

Endothelial nitric oxide synthase mediates the nitric oxide component of reflex cutaneous vasodilatation during dynamic exercise in humans.

Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental V̇O2, peak test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: (1) lactated Ringer's (control); (2) 20 mm Nω-nitro-l-arginine methyl ester hydrochloride (non-selective NOS inhibitor); (3) 5 mm N-propyl-l-arginine (nNOS inhibitor); and (4) 10 mm N(5)-(1-iminoethyl)-l-ornithine dihydrochloride [endothelial NOS (eNOS) inhibitor]. Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% V̇O2, peak for a period sufficient to raise core temperature 0.8°C. At the end of cycling, all microdialysis sites were locally heated to 43°C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure, skin blood flow via laser-Doppler flowmetry and core temperature via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as laser-Doppler flowmetry/mean arterial pressure and normalized to maximum. There was no significant difference between control (58 ± 2%CVCmax) and nNOS-inhibited (56 ± 3%CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 ± 3%CVCmax) and non-selective NOS-inhibited (40 ± 4%CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P < 0.001 all conditions) but there was no difference between eNOS-inhibited and non-selective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with sustained dynamic exercise.

Exercise training and vascular cell phenotype in a swine model of familial hypercholesterolaemia: conduit arteries and veins.

NEW FINDINGS: What is the central question of this study? Does endurance exercise training cause anti-atherogenic effects on the endothelium in a swine model of familial hypercholesterolaemia (FH), and how are these effects distributed across veins, arteries and multiple vascular territories within each system? What is the main finding and its importance? Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control animals, and exercise training did not change vasomotor function within FH. In systemic conduit arteries and veins, few effects of FH on endothelial cell protein expression were noted, including both pro- and anti-atherogenic changes. These findings suggest that exercise training does not produce a consistently improved endothelial cell phenotype in either coronary or systemic conduit vessels in this swine model of FH. Exercise training has emerged as an intervention for the primary and secondary prevention of coronary artery disease, but the mechanisms through which training reduces relative risk are not completely understood. The goal of this study was to investigate the impact of endurance exercise training on vasomotor function and vascular cell phenotype in coronary arteries and systemic conduit arteries and veins against a background of advanced atherosclerosis. We tested the hypothesis that exercise training restores endothelial vasomotor function and produces an anti-atherogenic endothelial and smooth muscle cell phenotype in familial hypercholesterolaemic (FH) swine. The study included 30 FH (15 exercised and 15 sedentary) and 13 non-FH control male castrated swine. The exercise-training intervention consisted of treadmill running 5 days per week for 16-20 weeks. Tissues sampled at sacrifice included vascular rings from the coronary circulation for vasomotor function experiments (dose-dependent bradykinin-induced vasorelaxation) and endothelial cells (ECs) from isolated segments of the thoracic aorta, the carotid, brachial, femoral and renal arteries, as well as each corresponding regionally associated vein, and from the abdominal vena cava, the right coronary and internal mammary arteries. Smooth muscle cells were sampled from the right coronary artery only. Vascular cell phenotype was assessed by immunoblotting for a host of both pro- and anti-atherogenic markers [e.g. endothelial nitric oxide synthase, p67phox, superoxide dismutase 1 (SOD1)]. Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH pigs compared with sedentary control pigs, and exercise training did not change vasomotor function within FH. In contrast, only scattered effects of FH on EC phenotype were noted across the vasculature, which included both pro- and anti-atherogenic changes in EC protein expression (e.g. increased endothelial nitric oxide synthase in carotid artery ECs, decreased p67phox in brachial artery ECs, but decreased expression of the antioxidant protein SOD1 in thoracic vena cava; all P < 0.05). In thoracic vena cava ECs, this deficit was corrected by exercise training, while no other effects of exercise were observed in conduit vessel EC phenotype. Thus, while exercise training abrogated the adverse effect of hypercholesterolaemia on thoracic vena cava SOD1 expression, it appears that exercise training does not produce a consistently improved EC phenotype in either coronary or systemic conduit vessels in this FH swine model.

Involvement of the N-terminal B-box domain of Arabidopsis BBX32 protein in interaction with soybean BBX62 protein.

Previous studies have demonstrated that Arabidopsis thaliana BBX32 (AtBBX32) represses light signaling in A. thaliana and that expression of AtBBX32 in soybean increases grain yield in multiple locations and multiyear field trials. The BBX32 protein is a member of the B-box zinc finger family from A. thaliana and contains a single conserved Zn(2+)-binding B-box domain at the N terminus. Although the B-box domain is predicted to be involved in protein-protein interactions, the mechanism of interaction is poorly understood. Here, we provide in vitro and in vivo evidence demonstrating the physical and functional interactions of AtBBX32 with another B-box protein, soybean BBX62 (GmBBX62). Deletion analysis and characterization of the purified B-box domain indicate that the N-terminal B-box region of AtBBX32 interacts with GmBBX62. Computational modeling and site-directed mutagenesis of the AtBBX32 B-box region identified specific residues as critical for mediating the interaction between AtBBX32 and GmBBX62. This study defines the plant B-box as a protein interaction domain and offers novel insight into its role in mediating specific protein-protein interactions between different plant B-box proteins.

Cholinergic nerve contribution to cutaneous active vasodilation during exercise is similar to whole body passive heating.

Sympathetic cholinergic nerve cotransmission is widely accepted as the mechanism of cutaneous active vasodilation (CAVD) during whole body passive heating (passive heating). However, recent research suggests that there may be mechanistic differences in CAVD to heating, depending on the modality of thermal loading. It is unknown whether sympathetic cholinergic cotransmission explains CAVD during exercise. This study sought to confirm the role of cholinergic nerves in CAVD during passive heating and expand these findings to exercise. It was hypothesized that CAVD during both exercise and passive heating would be abolished by cholinergic nerve blockade. Eight young (18-30 yr) recreationally active individuals exercised (1 h seated cycling at 60% V̇o2peak) and were passively heated (∼1 h seated passive heating with mean skin temperature clamped at 39°C by water-perfused suit), in randomized order on separate days. Cholinergic nerves were blocked via Botox ∼2 wk prior to the study. Skin blood flow was assessed using laser Doppler flowmetry and expressed as percent of maximum cutaneous vascular conductance (%CVCmax). At the end of exercise/passive heating, internal temperature had increased by ∼0.7°C. The %CVCmax at the Botox-treated sites (exercise: 19 ± 6 and passive heating: 15 ± 14%CVCmax) was significantly less (P < 0.001) than at the untreated sites (exercise: 35 ± 11 and passive heating: 38 ± 6%CVCmax), but there were no differences between exercise and passive heating (modality, P = 0.909; modality-Botox interaction, P = 0.230). We conclude that CAVD during both exercise and passive heating is mediated by sympathetic cholinergic nerves, a critical thermoregulatory mechanism that appears to be independent of the thermal loading modality.NEW & NOTEWORTHY Our study establishes the primacy of cholinergic nerves to cutaneous active vasodilation during exercise and confirms this model during passive heating using a crossover study design. In addition, the mode of heating, whether passive or exercise induced, did not change the sensitivity of the cholinergic component of the thermoeffector response to increased internal temperature. Thus, cutaneous active vasodilator nerves are responsible for similar skin blood flow responses regardless of how thermal loading is accomplished.

Vascular effects of exercise: endothelial adaptations beyond active muscle beds.

Endothelial adaptations to exercise training are not exclusively conferred within the active muscle beds. Herein, we summarize key studies that have evaluated the impact of chronic exercise on the endothelium of vasculatures perfusing nonworking skeletal muscle, brain, viscera, and skin, concluding with discussion of potential mechanisms driving these endothelial adaptations.

Heterogeneity of endothelial cell phenotype within and amongst conduit vessels of the swine vasculature.

The purpose of this study was to investigate the extent of endothelial cell phenotypic heterogeneity throughout the swine vasculature, with a focus on the conduit vessels of the arterial and venous circulations. We tested the hypothesis that atheroprone arteries exhibit higher expression of markers of inflammation and oxidative stress than do veins and atheroresistant arteries. The study sample included tissues from 79 castrated, male swine. Immediately after the animals were killed, endothelial cells were mechanically scraped from isolated segments of the thoracic and abdominal aorta, carotid, brachial, femoral and renal arteries, and the vein regionally associated with each of these vessels, as well as the internal mammary and right coronary arteries. Cells were also taken from two regions of the aortic arch contrasted by atheroprone versus atherosusceptible haemodynamics. Endothelial cell phenotype was assessed by either immunoblotting or quantitative real-time PCR for a host of both pro- and anti-atherogenic markers (e.g. endothelial nitric oxide synthase, p67phox, cyclo-oxygenase-1 and superoxide dismutase 1). Marked heterogeneity across the vasculature was observed in the expression of both pro- and anti-atherogenic markers, at both the protein and transcriptional levels. In particular, the coronary vascular endothelium expressed higher levels of the oxidative stress marker p67phox (P < 0.05 versus other arteries). In addition, differential expression of endothelial nitric oxide synthase and KLF4 was evident between atheroprone and atherosusceptible regions of the aorta, while expression of endothelial nitric oxide synthase, KLF2, KLF4 and cyclo-oxygenase-1 was lower in both areas of the aortic arch compared with the internal mammary artery. Conduit arteries typically expressed higher levels of both pro- and anti-atherogenic markers relative to their associated veins. We show, for the first time, that endothelial cell phenotype is variable within vessels, across six major vascular territories, and between the arterial and venous circulations. Importantly, even straight vessel segments from systemic conduit arteries (e.g. brachial and carotid arteries) exhibited regional phenotypic heterogeneity; a finding not expected on the basis of local haemodynamic forces alone.

Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis.

While the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise trained for 16-20 wk (n = 8) and a group that remained sedentary (n = 8). We found that a total of 130 genes were upregulated and 84 genes downregulated in brachial artery endothelial cells with exercise training (>1.5-fold and false discovery rate <15%). In contrast, a total of 113 genes were upregulated and 31 genes downregulated in internal mammary artery endothelial cells using the same criteria. Although there was an overlap of 66 genes (59 upregulated and 7 downregulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature.

Changes in the control of skin blood flow with exercise training: where do cutaneous vascular adaptations fit in?

Heat is the most abundant byproduct of cellular metabolism. As such, dynamic exercise in which a significant percentage of muscle mass is engaged generates thermoregulatory demands that are met in part by increases in skin blood flow. Increased skin blood flow during exercise adds to the demands on cardiac output and confers additional circulatory strain beyond that associated with perfusion of active muscle alone. Endurance exercise training results in a number of physiological adaptations which ultimately reduce circulatory strain and shift thermoregulatory control of skin blood flow to higher levels of blood flow for a given core temperature. In addition, exercise training induces peripheral vascular adaptations within the cutaneous microvasculature indicative of enhanced endothelium-dependent vasomotor function. However, it is not currently clear how (or if) these local vascular adaptations contribute to the beneficial changes in thermoregulatory control of skin blood flow following exercise training. The purpose of this Hot Topic Review is to synthesize the literature pertaining to exercise training-mediated changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow. In addition, we address mechanisms driving changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow, and pose the question: what (if any) is the functional role of increased cutaneous microvascular reactivity following exercise training?

Cutaneous vascular and core temperature responses to sustained cold exposure in hypoxia.

We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P < 0.05 versus precooling). Hypoxia caused vasodilatation prior to cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P < 0.05 versus precooling; both P < 0.05 versus normoxia). Core cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.

Brachial artery vasodilatation during prolonged lower limb exercise: role of shear rate.

We recently observed a marked increase in brachial artery (BA) diameter during prolonged leg cycling exercise. The purpose of the present study was to test the hypothesis that this increase in BA diameter during lower limb exercise is shear stress mediated. Accordingly, we determined whether recapitulation of cycling-induced BA shear rate with forearm heating, a known stimulus evoking shear-induced conduit artery dilatation, would elicit comparable profiles and magnitudes of BA vasodilatation to those observed during cycling. In 12 healthy men, BA diameter and blood velocity were measured simultaneously using Doppler ultrasonography at baseline and every 5 min during 60 min of either steady-state semi-recumbent leg cycling (120 W) or forearm heating. At the onset of cycling, the BA diameter was reduced (-3.9 ± 1.2% at 5 min; P < 0.05), but it subsequently increased throughout the remainder of the exercise bout (+15.1 ± 1.6% at 60 min; P < 0.05). The increase in BA diameter during exercise was accompanied by an approximately 2.5-fold rise in BA mean shear rate (P < 0.05). Similar increases in BA mean shear with forearm heating elicited an equivalent magnitude of BA vasodilatation to that observed during cycling (P > 0.05). Herein, we found that in the absence of exercise the extent of the BA vasodilator response was reproduced when the BA was exposed to comparable magnitudes of shear rate via forearm heating. These results are consistent with the hypothesis that shear stress plays a key role in signalling brachial artery vasodilatation during dynamic leg exercise.

Long-term exercise training does not alter brachial and femoral artery vasomotor function and endothelial phenotype in healthy pigs.

Although the beneficial effects of exercise training on conduit artery endothelial function are well-established in animals and humans with compromised basal function, whether exercise exerts favorable effects on a healthy endothelium is inconclusive. We sought to determine whether long-term exercise training enhances endothelial function in peripheral conduit arteries of healthy pigs. Using a retrospective analysis of data collected in our laboratory (n = 127), we compared in vitro brachial and femoral artery endothelium-dependent and -independent relaxation between a group of pigs that exercise-trained for 16-20 wk and a group that remained sedentary. No differences in vasomotor function were found between the 2 groups (P > 0.05). Additionally, in a subset of pigs (n = 16), expression levels of 18 proteins that are typically associated with the atherosclerotic process were measured by immunoblot analysis of endothelial cell scrapes obtained from the brachial and femoral arteries. We found no differences (P > 0.05) in endothelial gene expression between these exercise-trained and sedentary healthy pigs. These results indicate that pigs exhibiting the classic training-induced adaptations do not demonstrate enhanced endothelium-dependent dilation nor reveal a more atheroprotected endothelial cell phenotype in their brachial and femoral arteries than their sedentary but otherwise healthy counterparts.

Increased muscle sympathetic nerve activity acutely alters conduit artery shear rate patterns.

Escalating evidence indicates that disturbed flow patterns, characterized by the presence of retrograde and oscillatory shear stress, induce a proatherogenic endothelial cell phenotype; however, the mechanisms underlying oscillatory shear profiles in peripheral conduit arteries are not fully understood. We tested the hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are accompanied by increases in conduit artery retrograde and oscillatory shear. Fourteen healthy men (25 +/- 1 yr) performed three sympathoexcitatory maneuvers: graded lower body negative pressure (LBNP) from 0 to -40 Torr, cold pressor test (CPT), and 35% maximal voluntary contraction handgrip followed by postexercise ischemia (PEI). MSNA (microneurography; peroneal nerve), arterial blood pressure (finger photoplethysmography), and brachial artery velocity and diameter (duplex Doppler ultrasound) in the contralateral arm were recorded continuously. All maneuvers elicited significant increases in MSNA total activity from baseline (P < 0.05). Retrograde shear (-3.96 +/- 1.2 baseline vs. -8.15 +/- 1.8 s(-1), -40 LBNP, P < 0.05) and oscillatory shear index (0.09 +/- 0.02 baseline vs. 0.20 +/- 0.02 arbitrary units, -40 LBNP, P < 0.05) were progressively augmented during graded LBNP. In contrast, during CPT and PEI, in which MSNA and blood pressure were concomitantly increased (P < 0.05), minimal or no changes in retrograde and oscillatory shear were noted. These data suggest that acute elevations in MSNA are associated with an increase in conduit artery retrograde and oscillatory shear, an effect that may be influenced by concurrent increases in arterial blood pressure. Future studies should examine the complex interaction between MSNA, arterial blood pressure, and other potential modulatory factors of shear rate patterns.

Systemic hypoxia causes cutaneous vasodilation in healthy humans.

Hypoxia and hypercapnia represent special challenges to homeostasis because of their effects on sympathetic outflow and vascular smooth muscle. In the cutaneous vasculature, even small changes in perfusion can shift considerable blood volume to the periphery and thereby impact both blood pressure regulation and thermoregulation. However, little is known about the influence of hypoxia and hypercapnia on this circulation. In the present study, 35 healthy subjects were instrumented with two microdialysis fibers in the ventral forearm. Each site was continuously perfused with saline (control) or bretylium tosylate (10 mM) to prevent sympathetically mediated vasoconstriction. Skin blood flow was assessed at each site (laser-Doppler flowmetry), and cutaneous vascular conductance (CVC) was calculated as red blood cell flux/mean arterial pressure and normalized to baseline. In 13 subjects, isocapnic hypoxia (85 and 80% O(2) saturation) increased CVC to 120 +/- 10 and 126 +/- 7% baseline in the control site (both P < 0.05) and 113 +/- 3 (P = 0.087) and 121 +/- 4% baseline (P < 0.05) in the bretylium site. Adrenergic blockade did not affect the magnitude of this response (P > 0.05). In nine subjects, hyperpnea (matching hypoxic increases in tidal volume) caused no change in CVC in either site (both P > 0.05). In 13 subjects, hypercapnia (+5 and +9 Torr) increased CVC to 111 +/- 4 and 111 +/- 4% baseline, respectively, in the control site (both P < 0.05), whereas the bretylium site remained unchanged (both P > 0.05). Thus both hypoxia and hypercapnia cause modest vasodilation in nonacral skin. Adrenergic vasoconstriction of neural origin does not restrain hypoxic vasodilation, but may be important in hypercapnic vasodilation.

Duration of life-threatening antecedents prior to intensive care admission.

OBJECTIVE: To document the characteristics and incidence of serious abnormalities in patients prior to admission to intensive care units. DESIGN AND SETTING: Prospective follow-up study of all patients admitted to intensive care in three acute-care hospitals. PATIENTS: The study population totalled 551 patients admitted to intensive care: 90 from the general ward, 239 from operating rooms (OR) and 222 from the Emergency Department (ED). MEASUREMENTS AND RESULTS: Patients from the general wards had greater severity of illness (APACHE II median 21) than those from the OR (15) or ED (19). A greater percentage of patients from the general wards (47.6%) died than from OR (19.3%) and ED (31.5%). Patients from the general wards had a greater number of serious antecedents before admission to intensive care 43 (72%) than those from OR 150 (64.4%) or ED 126 (61.8%). Of the 551 patients 62 had antecedents during the period 8-48 h before admission to intensive care, and 53 had antecedents both within 8 and 48 h before their admission. The most common antecedents during the 8 h before admission were hypotension (n=199), tachycardia (n=73), tachypnoea (n=64), and sudden change in level of consciousness (n=42). Concern was expressed in the clinical notes by attending staff in 70% of patients admitted from the general wards. CONCLUSIONS: In over 60% of patients admitted to intensive care potentially life-threatening abnormalities were documented during the 8 h before their admission. This may represent a patient population who could benefit from improved resuscitation and care at an earlier stage.

Peripheral circulation.

Blood flow (BF) increases with increasing exercise intensity in skeletal, respiratory, and cardiac muscle. In humans during maximal exercise intensities, 85% to 90% of total cardiac output is distributed to skeletal and cardiac muscle. During exercise BF increases modestly and heterogeneously to brain and decreases in gastrointestinal, reproductive, and renal tissues and shows little to no change in skin. If the duration of exercise is sufficient to increase body/core temperature, skin BF is also increased in humans. Because blood pressure changes little during exercise, changes in distribution of BF with incremental exercise result from changes in vascular conductance. These changes in distribution of BF throughout the body contribute to decreases in mixed venous oxygen content, serve to supply adequate oxygen to the active skeletal muscles, and support metabolism of other tissues while maintaining homeostasis. This review discusses the response of the peripheral circulation of humans to acute and chronic dynamic exercise and mechanisms responsible for these responses. This is accomplished in the context of leading the reader on a tour through the peripheral circulation during dynamic exercise. During this tour, we consider what is known about how each vascular bed controls BF during exercise and how these control mechanisms are modified by chronic physical activity/exercise training. The tour ends by comparing responses of the systemic circulation to those of the pulmonary circulation relative to the effects of exercise on the regional distribution of BF and mechanisms responsible for control of resistance/conductance in the systemic and pulmonary circulations.

Impact of aging on conduit artery retrograde and oscillatory shear at rest and during exercise: role of nitric oxide.

Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries, a hemodynamic environment that favors a proatherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Younger (n=11, age 26 ± 2 years) and older (n=11, age 61 ± 2 years) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor N(G)-Monomethyl-L-arginine. Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-minute bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (-13.2 ± 3.0 s(-1) and 0.11 ± .0.02 arbitrary units, respectively) compared with young subjects (-4.8 ± 2.3 s(-1) and 0.04 ± 0.02 arbitrary units, respectively; both P<0.05). NO synthase inhibition in the forearm circulation of young, but not of older, subjects increased retrograde and oscillatory shear (both P<0.05), such that differences between young and old at rest were abolished (both P>0.05). From rest to steady-state exercise, older subjects decreased retrograde and oscillatory shear (both P<0.05) to the extent that no exercise-related differences were found between groups (both P>0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all P>0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries.