Basal Leg Blood Flow Research Articles

Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction.

Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (P < 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10-4 ± 2.0 × 10-4%/s-1, ET-1: 0.9 × 10-4 ± 2.8 ×10-4%/s-1). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter.NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.

Pulse wave velocity is associated with muscle mass decline: Health ABC study

Age-related mechanisms that lead to sarcopenia are not entirely understood. Basal leg blood flow declines with aging by augmented sympathetic vasoconstriction and arterial stiffening, thus a dysfunction in blood vessel dynamics may have an independent role on sarcopenia. We determined whether pulse wave velocity (PWV), marker of arterial stiffness, was associated with skeletal muscle decline. Observational cohort study of older adults(70-79 years) living in Pittsburgh, PA, USA or Memphis, TN, USA. Analyses included 2,405 participants. Correlations among muscle parameters including skeletal muscle density and intermuscular adipose tissue using mid-thigh CT scans were assessed. Linear mixed models tested the association between the change in the sarcopenic index (SI) (assessed by dual energy X-ray absorptiometry) over time and baseline PWV independently of multiple confounders. SI was defined: appendicular lean mass/squared height and calculated at every follow-up (n = 6). Baseline PWV was significantly higher in black women compared to white women (930 ± 431 vs. 843 ± 366; p = 0.0001), while there were no significant differences between black and white men (943 ± 402 vs. 911 ± 375; p = 0.1786). Baseline analyses showed an independent negative association between PWV and muscle parameters after adjusting for confounders in both genders. The PWV-by-race interaction was significant in women and analyses are reported separately by race. Prospective mixed models showed that PWV was an independent determinant of the SI in all men (β = -0.1043; p = 0.0065) and in white women (β = -0.1091; p = 0.0192). In analyses examining the effect of arterial stiffness on limb lean mass over time, PWV correlated with lower leg (β = -0.2196; p = 0.0002)and arm mass (β = -0.0985; p = 0.0011) in all men and lower leg mass(β = -0.1608; p = 0.0027)in white women. In older persons, arterial stiffening is associated with skeletal muscle mass decline differently for race and gender.

Effect of elastic-band-based resistance training on leg blood flow in elderly women

The age-related decline in basal limb blood flow appears to be related to the pathogenesis of metabolic syndrome, noninsulin-dependent diabetes, and cardiovascular disease. Resistance training improves basal limb blood flow and vascular conductance in middle-aged men and women, but it is unknown whether similar vascular effects of training occur in the elderly. This study aimed to examine the effects of a 12-week progressive resistance training program using elastic bands on basal leg blood flow, vascular conductance, and functional performance in postmenopausal elderly women. Sixteen healthy postmenopausal females (age, 67± 5 years) were randomly assigned to a control (n = 8) or resistance training (n = 8) group, where they underwent 2 supervised strength sessions per week for 12 weeks. Prior to and at completion of this 12-week period, functional and strength performance and leg haemodynamic responses were measured. The training intervention produced significant increases in basal leg blood flow (31%), vascular conductance (34%), and a significant reduction in cardiac work (i.e., rate pressure product) at rest, as well as significant improvements in the 3 functional ability tests performed (30-s bicep curl, 30-s sit to stand, and back scratch). Haemodynamic or functional performance responses were not altered after the 12 weeks in the control group. This study demonstrates that a resistance training program using elastic bands elicits significant improvements in basal leg blood flow in postmenopausal elderly women.

Habitual exercise and arterial aging

Aging affects the function and structure of arteries and increases the risk of cardiovascular diseases (CVD). In healthy sedentary adults, aging is associated with increased stiffness (reduced compliance) of large elastic arteries; impaired vascular endothelial function, including reductions in endothelium-dependent dilation (EDD), release of tissue-type plasminogen activator (fibrinolytic capacity) and endothelial progenitor cell number and function; increased intima-media wall thickness (IMT); and peripheral vasoconstriction (decreased basal leg blood flow). Habitual physical activity/increased aerobic exercise capacity is associated with reduced risk of CVD. Compared with their sedentary peers, adults who regularly perform aerobic exercise demonstrate smaller or no age-associated increases in large elastic artery stiffness, reductions in vascular endothelial function, and increases in femoral artery IMT. A short-term, moderate-intensity aerobic exercise intervention (brisk daily walking for 12 wk) improves carotid artery compliance and can restore vascular endothelial function in previously sedentary middle-aged and older adults. Reduced oxidative stress may be an important mechanism contributing to these effects. Habitual resistance exercise increases (high-intensity) or does not affect (moderate-intensity) large elastic artery stiffness, and prevents/restores the age-associated reduction in basal leg blood flow independent of changes in leg fat-free mass. Habitual exercise favorably modulates several expressions of arterial aging, thus preserving vascular function and possibly reducing the risk of CVD.

Systemic α-adrenergic and nitric oxide inhibition on basal limb blood flow: effects of endurance training in middle-aged and older adults

Endurance training improves endothelium-dependent vasodilation, yet it does not increase basal blood flow in the legs. We determined the effects of a 3-mo aerobic exercise intervention on basal leg blood flow and alpha-adrenergic vasoconstriction and nitric oxide (NO) release in seven apparently healthy middle-aged and older adults (60 +/- 3 yr). Basal femoral artery blood flow (via Doppler ultrasound) (pretraining: 354 +/- 29; posttraining: 335 +/- 34 ml/min) and vascular conductance did not change significantly with the exercise training. Before the exercise intervention, femoral artery blood flow increased 32 +/- 16% with systemic alpha-adrenergic blockade (with phentolamine) (P < 0.05), and the addition of nitric oxide synthase (NOS) inhibition using N(G)-monomethyl-L-arginine (L-NMMA) did not affect femoral artery blood flow. After training was completed, femoral artery blood flow increased 47 +/- 7% with alpha-adrenergic blockade (P < 0.01) and then decreased 18 +/- 7% with the subsequent administration of L-NMMA (P < 0.05). Leg vascular conductance showed a greater alpha-adrenergic blockade-induced vasodilation (+1.7 +/- 0.5 to +3.0 +/- 0.5 units, P < 0.05) as well as NOS inhibition-induced vasoconstriction (-0.8 +/- 0.4 to -2.7 +/- 0.7 units, P < 0.05) after the exercise intervention. Resting plasma norepinephrine concentration significantly increased after the training. These results suggest that regular aerobic exercise training enhances NO bioavailability in middle-aged and older adults and that basal limb blood flow does not change with exercise training because of the contrasting influences of sympathetic nervous system activity and endothelium-derived vasodilation on the vasculature.

Systemic α-adrenergic and Nitric Oxide Inhibition on Basal Limb Blood Flow before and after Endurance Training in Aging Humans

PURPOSE: Endurance training improves endothelium-dependent vasodilation. Yet it does not increase basal leg blood flow. We determined effects of endurance training on basal blood flow and α-adrenergic vasoconstriction and nitric oxide release in aged humans. METHODS: Seven apparently healthy adults (60±3 yr) underwent systemic α-adrenergic blockade (with phentolamine) and nitric oxide synthase (NOS) inhibition using NG-monomethyl-L-arginine in sequence before and after the 3-month aerobic exercise intervention. RESULTS: Baseline femoral artery blood flow (via Doppler ultrasound) did not change significantly with the exercise training intervention (354±29 to 335±34 ml/ min). Before the training intervention, femoral artery blood flow increased 32% with α-adrenergic blockade (P<0.05), and the addition of NOS blockade did not affect femoral artery blood flow (ns). After the training intervention, femoral artery blood flow increased 47% with ?-adrenergic blockade (P<0.01) and then reduced 18±7% with L-NMMA administration (P<0.05). Leg vascular conductance showed a greater α-adrenergic blockade-induced vasodilation (50±16 to 86±13%, P<0.05) as well as NOS inhibition-induced vasoconstriction (−15±8 to −38±7%, P<0.05) after the training. CONCLUSIONS: These results suggest that endurance training enhances both basal α-adrenergic vasoconstriction and NO bioavailability in older adults and that basal limb blood flow does not change with exercise training because of these antagonistic effects of sympathetic activation and endothelium-derived vasodilation on the vasculature.

Oxidative stress contributes to the age related decline in basal leg blood flow in sedentary men

Oxidative stress contributes to the age related decline in basal leg blood flow in sedentary men

Combined inhibition of NO, prostaglandins and EDHFs inhibits ATP‐induced vasodilation in the human leg

Adenosine-5′-triphosphate (ATP) can bind to P2y-purinergicreceptors and induce vasodilation in skeletal muscle, but the precise mechanisms by which this occurs remain unclear. To investigate whether ATP induced vasodilation is mediated by the action of nitric oxide (NO), prostaglandins and/or endothelial-derived hyperpolarizing factors (EDHFs), we measured leg hemodynamics before and during 5 min of intra-arterial infusion of ATP (0.41±0.04μmol min−1;mean±SEM) in 8 healthy, male subjects (24±2 years, 76±3 kg) with and without co-infusion of indomethacin (INDO; 621±17 μg min−1), NG-mono-methyl-L-arginine (L-NMMA; 12.4±0.3 mg min−1), tetraethylammonium chloride (TEA; 12.4±0.3 mg min−1) or INDO + L-NMMA + TEA. Basal leg blood flow (LBF) was 0.46±0.06 l min−1, but was lower with either L-NMMA (0.32±0.03) or all three inhibitors (0.28±0.06)(P<0.05), whereas infusion of either TEA or INDO had no effect on basal flow. ATP infusion increased LBF to 2.4±0.2 l min−1, but with co-infusion of either INDO or L-NMMA alone, or all three inhibitors combined, it was 13±8, 22±8 and 39±5 % lower, respectively, than with ATP infusion alone. Infusion of TEA did not alter the ATP induced hyperemia. The lower LBF with ATP combined with INDO, L-NMMA and triple blockade was associated with a 8–12% higher blood pressure and a 15–45 % lower vascular conductance, while heart rate and leg VO2 remained similar. These results indicate that both NO and prostaglandins play an important role in ATP mediated vasodilatation, whereas EDHFs appear to be less important. Supported by Lundbeck Foundation

Lack of age-related decreases in basal whole leg blood flow in resistance-trained men

Reductions in basal leg blood flow have been implicated in the pathogenesis of metabolic syndrome and functional impairment in humans. We tested the hypothesis that reductions in basal whole leg blood flow with age are either absent or attenuated in those who perform regular strength training. A total of 104 normotensive men aged 20-34 yr (young) and 35-65 yr (middle aged), who were either sedentary or resistance trained, were studied. Mean and diastolic blood pressures were higher (P < 0.05-0.001) in the middle-aged compared with the young men, but there were no significant differences between the sedentary and resistance-trained groups. In the sedentary group, basal whole leg blood flow (duplex Doppler ultrasound) and vascular conductance were lower ( approximately 30 and approximately 38%, respectively; P < 0.01) in the middle-aged compared with the young men. There were no such age-related differences in the resistance-trained group. In the young men, basal whole leg blood flow and vascular conductance were not different between the two activity groups, but, in the middle-aged men, they were higher ( approximately 35 and approximately 36%, respectively; P < 0.01) in the resistance-trained men than in the sedentary men. When blood flow and vascular conductance were expressed relative to the leg muscle mass, the results were essentially the same. We concluded that the age-related reduction in basal whole leg blood flow is absent in resistance-trained men. These results suggest that resistance training may favorably influence leg perfusion in aging humans, independent of its impact on leg muscle mass.

Reductions in Basal Blood Flow and Arterial Remodeling after Short-Term Leg Immobilization

0375 PURPOSE: We tested the hypothesis that short-term immobilization of leg with casting would reduce basal leg blood flow and vascular conductance and induce structural alterations in femoral artery. METHODS: Right knee and ankle joints of 8 young healthy men (22 ± 1 yr) were immobilized with casting for 7 days. Before, immediately after, and 14 days after the immobilization, femoral artery function and structure were measured using a duplex ultrasound. RESULTS: Arterial blood pressure and leg circumference did not change throughout the study. Femoral artery lumen diameter in the immobilized leg decreased after the immobilization (p < 0.05) and returned to baseline during the recovery period, in which the subjects did not receive any rehabilitation treatment. Femoral artery intima-media thickness (IMT) and IMT/lumen ratio in both legs did not show significant changes throughout the interventions. In the immobilized leg, femoral artery blood flow and vascular conductance decreased (−23 to 24%) after the immobilization (all p < 0.05). These parameters returned to the baseline during the recovery period, and there were no significant differences between the baseline and recovery values. In the control leg, femoral blood flow, vascular conductance, and vascular resistance did not change throughout the investigation. After 7 days of casting, femoral arterial expansion rate, an index of arterial distensibility, tended to decrease in the immobilized leg but not in the control leg. CONCLUSION: A short-term immobilization of lower limb decreases basal limb blood flow and induces inward, eutrophic remodeling. These results suggest that disuse-induced reductions in blood flow may occur prior to muscle atrophy and that basal limb blood flow may be modulated by an ordinary level of physical activity.

Reductions in Basal Blood Flow and Arterial Remodeling after Short-Term Leg Immobilization

0375 PURPOSE: We tested the hypothesis that short-term immobilization of leg with casting would reduce basal leg blood flow and vascular conductance and induce structural alterations in femoral artery. METHODS: Right knee and ankle joints of 8 young healthy men (22 ± 1 yr) were immobilized with casting for 7 days. Before, immediately after, and 14 days after the immobilization, femoral artery function and structure were measured using a duplex ultrasound. RESULTS: Arterial blood pressure and leg circumference did not change throughout the study. Femoral artery lumen diameter in the immobilized leg decreased after the immobilization (p < 0.05) and returned to baseline during the recovery period, in which the subjects did not receive any rehabilitation treatment. Femoral artery intima-media thickness (IMT) and IMT/lumen ratio in both legs did not show significant changes throughout the interventions. In the immobilized leg, femoral artery blood flow and vascular conductance decreased (−23 to 24%) after the immobilization (all p < 0.05). These parameters returned to the baseline during the recovery period, and there were no significant differences between the baseline and recovery values. In the control leg, femoral blood flow, vascular conductance, and vascular resistance did not change throughout the investigation. After 7 days of casting, femoral arterial expansion rate, an index of arterial distensibility, tended to decrease in the immobilized leg but not in the control leg. CONCLUSION: A short-term immobilization of lower limb decreases basal limb blood flow and induces inward, eutrophic remodeling. These results suggest that disuse-induced reductions in blood flow may occur prior to muscle atrophy and that basal limb blood flow may be modulated by an ordinary level of physical activity.

Basal leg blood flow in healthy women is related to age and hormone replacement therapy status

Graphical Abstract Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function of hyperpolarization-activated cation (HCN) channels in smooth muscle pacemakers remains controversial. Renal pelvic smooth muscle pacemakers trigger smooth muscle contractions that expel waste from the kidney, and HCN channels have been localized to these pacemaker tissues. To date, however, the mechanisms underlying RPSM pacemaker activity remain elusive. RPSM pacemaker activity was investigated in both lower (top left) and higher order (bottom left) mammalian models, which exhibit divergent upper urinary tract anatomies. We performed morphological and functional studies from the single-molecule to the whole-organ level and showed that HCN channels drive RPSM pacemaker activity. RPSM pacemakers (boxed regions) integrated into the muscular syncytium, expressed HCN channels on their plasmalemma and exhibited the Ih ‘funny’ pacemaker current conducted by HCN channels. Critically, HCN channel block abolished electrical pacemaker activity and peristaltic smooth muscle contractions in both lower and higher order mammalian upper urinary tracts. Thus, HCN channels play an evolutionarily conserved pacemaker role in RPSM pacemakers.