Increase In Leg Vascular Conductance Research Articles

Skeletal muscle microvascular insulin resistance in type 2 diabetes is not improved by eight weeks of regular walking.

We aimed to examine whether individuals with type 2 diabetes (T2D) exhibit suppressed leg vascular conductance and skeletal muscle capillary perfusion in response to a hyperinsulinemic-euglycemic clamp and to test whether these two variables are positively correlated. Subsequently, we examined whether T2D-associated skeletal muscle microvascular insulin resistance, as well as overall vascular dysfunction, would be ameliorated by an 8-wk walking intervention (45 min at 60% of heart rate reserve, 5 sessions/week). We report that, relative to healthy subjects, overweight and obese individuals with T2D exhibit depressed insulin-stimulated increases in leg vascular conductance, skeletal muscle capillary perfusion, and Akt phosphorylation. Notably, we found that within individuals with T2D, those with lesser increases in leg vascular conductance in response to insulin exhibited the lowest increases in muscle capillary perfusion, suggesting that limited muscle capillary perfusion may be, in part, linked to the impaired ability of the upstream resistance vessels to dilate in response to insulin. Furthermore, we show that the 8-wk walking intervention, which did not evoke weight loss, was insufficient to ameliorate skeletal muscle microvascular insulin resistance in previously sedentary, overweight/obese subjects with T2D, despite high adherence and tolerance. However, the walking intervention did improve (P < 0.05) popliteal artery flow-mediated dilation (+4.52%) and reduced HbA1c (-0.75%). It is possible that physical activity interventions that are longer in duration, engage large muscle groups with recruitment of the maximum number of muscle fibers, and lead to a robust reduction in metabolic risk factors may be required to overhaul microvascular insulin resistance in T2D.NEW & NOTEWORTHY This report provides evidence that in sedentary subjects with type 2 diabetes diminished insulin-stimulated increases in leg vascular conductance and ensuing blunted capillary perfusion in skeletal muscle are not restorable by increased walking alone. More innovative physical activity interventions that ultimately result in a robust mitigation of metabolic risk factors may be vital for reestablishing skeletal muscle microvascular insulin sensitivity in type 2 diabetes.

Attenuated Leg Vascular Conductance Responses To Dynamic Knee Extension Exercise In Young Black Men

Our group recently showed a blunted increase in skeletal muscle vascular conductance and blood flow during rhythmic handgrip exercise in young black (i.e. African American) individuals with no overt cardiovascular diseases compared with white (i.e. Caucasian American) individuals. These findings, along with reduced endothelium‐dependent forearm vasodilation and augmented forearm vasoconstriction to phenylephrine at rest, suggest that vascular alterations occur early in the lifetime of black individuals, possibly predisposing this population to develop cardiovascular diseases. Notably, research on racial differences in vascular responses has almost exclusively examined upper limbs. However, lower limb vascular diseases are more prevalent and cause more adverse events in the black population than in any other racial group in the U.S. Therefore, for a better understanding of racial differences in vascular health, we tested the hypothesis that vascular responses to lower limb exercise would be attenuated in black individuals compared with their white counterparts. Six black (21 ± 1 years; 23 ± 2 kg/m2) and 4 white (21 ± 0 years; 21 ± 1 kg/m2) healthy men performed dynamic knee extension exercise at the workloads of 10, 20, and 30 watts (W) in an upright sitting position on a custom ergometer. Each exercise trial lasted for 3 min with a minimum rest interval of 5 min. Knee extension cadence was 50 repetitions per min, provided by a metronome and real‐time visual feedback. Common femoral artery blood flow (FABF, Doppler ultrasound) and mean arterial pressure (MAP, finger photoplethysmography) were continuously measured, and leg vascular conductance (LVC) was calculated as FABF/MAP. The participants reported a rating of perceived exertion (Borg Scale 6 – 20) at the end of each trial. Both groups presented LVC increases from rest during dynamic knee extension. While this response was similar between groups at 10 W (White: +1970 ± 138 vs. Black: +1666 ± 173 mL/min/100 mmHg; P = 0.407), the increases in LVC were significantly attenuated in black individuals (mixed‐model ANOVA interaction P = 0.026) at the workloads of 20 W (Whites: +2550 ± 105 vs. Blacks: +1829 ± 179 mL/min/100 mmHg; P = 0.025) and 30 W (Whites: +2528 ± 248 vs. Blacks: +1850 ± 152 mL/min/100 mmHg; P = 0.035). Similarly, FABF responses to dynamic knee extension were lower in black individuals compared with their white counterparts (Interaction P = 0.011). In contrast, increases in MAP were similar between groups (Interaction P = 0.271). The groups reported similar ratings of perceived exertion among trials (Interaction P = 0.817) and achieved similar peak workloads in a dynamic knee extension maximal exercise test (Whites: 48 ± 8 W vs. Blacks: 49 ± 3 W; P = 0.883). These preliminary findings suggest a blunted vasodilator response during leg exercise in black men, further highlighting the early occurrence of vascular alterations in this population.Support or Funding InformationUTA Center of Research and Scholarship Pilot Grant;NIH (1R15HL130906‐01)

Physiological adaptations to resistance exercise as a function of age.

BACKGROUND. The impact of resistance exercise training (RE-T) across the life span is poorly defined.METHODS. To resolve this, we recruited three distinct age cohorts of young (18–28 years; n = 11), middle-aged (45–55 years; n = 20), and older (nonsarcopenic; 65–75 years; n = 17) individuals to a cross-sectional intervention study. All subjects participated in 20 weeks of fully supervised whole-body progressive RE-T, undergoing assessment of body composition, muscle and vascular function, and metabolic health biomarkers before and after RE-T. Individuals also received stable isotope tracer infusions to ascertain muscle protein synthesis (MPS).RESULTS. There was an age-related increase in adiposity, but only young and middle-age groups demonstrated reductions following RE-T. Increases in blood pressure with age were attenuated by RE-T in middle-aged, but not older, individuals, while age-related increases in leg vascular conductance were unaffected by RE-T. The index of insulin sensitivity was reduced by RE-T in older age. Despite being matched at baseline, only younger individuals increased muscle mass in response to RE-T, and there existed a negative correlation between age and muscle growth; in contrast, increases in mechanical quality were preserved across ages. Acute increases in MPS (upon feeding plus acute RE-T) were enhanced only in younger individuals, perhaps explaining greater hypertrophy.CONCLUSION. Our data indicate that RE-T offsets some, but not all, negative characteristics of ageing — some of which are apparent in midlife.FUNDING. Biotechnology and Biological Sciences Research Council (BB/C516779/1).

Group III/IV muscle afferents impair limb blood in patients with chronic heart failure

ObjectiveTo better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise. MethodsNine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27±3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. ResultsCardiac-output (Q) and femoral blood-flow (QL) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8–13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p<0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10–14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p<0.05). Conclusion/practice/implicationsAlthough group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.

Group III/IV muscle afferents impair limb blood flow during exercise in patients with heart failure

Patients with heart failure (HF) are characterized by altered muscle afferent feedback which might account for their hemodynamic and autonomic reflex abnormalities. We investigated the influence of group III/IV muscle afferents on the circulatory response to rhythmic exercise in HF. Nine patients (NYHA class II) performed single leg knee extensor exercise (25/50/80% peak workload) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ‐opioid receptor‐sensitive muscle afferents. Cardiac output (Q) and femoral blood flow (QL) were determined, and arterial/venous blood samples were collected at each workload. Fentanyl had no effect at rest. During exercise, Q was 8–13% lower with Fentanyl, secondary to a 13% reduction in stroke volume and a 2–5% reduction in heart rate. Lower norepinephrine spillover during Fentanyl exercise implicated a reduced sympathetic outflow and likely accounted for the 25% increase in leg vascular conductance. As a result of this attenuated sympathoexcitation, QL was, despite a 4% lower blood pressure, 10–14% higher during exercise with Fentanyl. Although leg O2 delivery was higher during exercise with Fentanyl, arteriovenous O2 difference remained unchanged resulting in 10–17% increase in leg O2 consumption (p&lt;0.05). Thus, although group III/IV muscle afferents represent a key determinant of the central hemodynamic response in HF, our findings also reveal that these sensory neurons cause a sympathetically‐mediated impairment of QL during rhythmic exercise in this population.

Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, -2.9 ± 1.1%; and multiple bursts, -11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

Effects of losartan on whole body, skeletal muscle and vascular insulin responses in obesity/insulin resistance without hypertension

Renin-angiotensin system antagonists have been found to improve glucose metabolism in obese hypertensive and type 2 diabetic subjects. The mechanism of these effects is not well understood. We hypothesized that the angiotensin receptor antagonist losartan would improve insulin-mediated vasodilation, and thereby improve insulin-stimulated glucose uptake in skeletal muscle of insulin-resistant subjects. We studied subjects with obesity and insulin resistance but without hypertension, hypercholesterolaemia or dysglycaemia [age 39.0 ± 9.6 yr (mean ± SD), body mass index (BMI) 33.2 ± 5.9 kg/m(2) , BP 115.8 ± 12.2/70.9 ± 7.2 mmHg, LDL 2.1 ± 0.5 mmol/l]. Subjects were randomized to 12 weeks' double-blind treatment with losartan 100 mg once daily (n = 9) or matching placebo (n = 8). Before and after treatment, under hyperinsulinaemic euglycaemic clamp conditions we measured whole-body insulin-stimulated glucose disposal, insulin-mediated vasodilation, and insulin-stimulated leg glucose uptake by the limb balance technique. Whole-body insulin-stimulated glucose disposal was not significantly increased by losartan. Insulin-mediated vasodilation was augmented following both treatments [increase in leg vascular conductance: pretreatment 0.7 ± 0.3 l/min/mmHg (losartan, mean ± SEM) and 0.9 ± 0.3 (placebo), posttreatment 1.0 ± 0.4 (losartan) and 1.3 ± 0.6 (placebo)] but not different between treatment groups (p = 0.53). Insulin's action to augment nitric oxide (NO) production and to augment endothelium-dependent vasodilation was also not improved. Leg glucose uptake was not significantly changed by treatments, and not different between groups (p = 0.11). These findings argue against the hypothesis that losartan might improve skeletal muscle glucose metabolism by improving insulin-mediated vasodilation in normotensive insulin-resistant obese subjects. The metabolic benefits of angiotensin receptor blockers may require the presence of hypertension in addition to obesity-associated insulin resistance.

Lower limb-localized vascular phenomena explain initial orthostatic hypotension upon standing from squat

The cause(s) of initial orthostatic hypotension (transient fall in blood pressure within 15 s upon active rising) have not been established. We tested the hypothesis that this hypotension is due to local vascular phenomena in contracting leg muscles from the brief effort of standing up. Seventeen young healthy subjects (2 male and 15 female, 22.5 ± 1.0 years) performed an active rise from resting squat after a 10-s squat, a 1-min squat, or a 5-min squat. Beat-by-beat arterial blood pressure, cardiac output, heart rate, and stroke volume (Finometer finger photoplethysmography) and right common femoral artery blood flow (Doppler and Echo ultrasound) were recorded. Data are means ± SE. Quiet standing before squat represented baseline. Peak increases in lower limb and total vascular conductance (ml·min(-1)·mmHg(-1)) upon standing were not different within squat conditions (10-s squat, 50.0 ± 12.4 vs. 44.3 ± 5.0; 1-min squat, 54.7 ± 9.2 vs. 50.5 ± 4.5; 5-min squat, 67.4 ± 13.7 vs. 58.8 ± 3.9; all P > 0.574). Mean arterial blood pressure (in mmHg) fell to a nadir well below standing baseline in all conditions despite increases in cardiac output. The hypotension predicted by the increase in leg vascular conductance accounted for this hypotension [observed vs. predicted (in mmHg): 10-s squat, -17.1 ± 2.1 vs. -18.3 ± 5.5; 1-min squat, -22.0 ± 3.8 vs. -25.3 ± 4.9; 5-min squat, -28.3 ± 4.0 vs. -29.2 ± 6.7]. We conclude that rapid contraction induced dilation in leg muscles with the effort of standing, along with a minor potential contribution of elevated lower limb arterio-venous pressure gradient, outstrips compensatory cardiac output responses and is the cause of initial orthostatic hypotension upon standing from squat.

Blunted increases in leg vascular conductance to carotid baroreflex activation in young women

The arterial baroreflex plays a critical role in the beat-to-beat regulation of arterial blood pressure (BP) primarily via reflex modulation of sympathetic nerve activity and vascular conductance. Limited studies focusing on sex differences have reported similar sympathetic baroreflex sensitivity at rest between young normotensive men and women. These data are interesting given recent evidence suggesting that resting arterial BP is differentially regulated in young men and women. Importantly, while the overall baroreflex control of muscle sympathetic nerve activity is critical, the actual vascular response evoked by baroreflex-mediated alterations in sympathetic nerve activity is essential for the ultimate control of BP.

Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women

Basal whole leg blood flow and vascular conductance are reduced in estrogen-deficient postmenopausal compared with premenopausal women. The underlying mechanisms are unknown, but oxidative stress could be involved. We studied 9 premenopausal [23 +/- 1 yr (mean +/- SE)] and 20 estrogen-deficient postmenopausal (55 +/- 1 yr) healthy women. During baseline control, oxidized low-density lipoprotein (LDL), a marker of oxidative stress, was 50% greater in the postmenopausal women (P < 0.001). Basal whole leg blood flow (duplex ultrasound of femoral artery) was 34% lower in the postmenopausal women because of a 38% lower leg vascular conductance (P < 0.0001); mean arterial pressure was not different. Intravenous administration of a supraphysiological dose of the antioxidant ascorbic acid increased leg blood flow by 15% in the postmenopausal women as a result of an increase in leg vascular conductance (both P < 0.001), but it did not affect leg blood flow in premenopausal controls or mean arterial pressure in either group. In the pooled subjects, the changes in leg blood flow and leg vascular conductance with ascorbic acid were related to baseline plasma oxidized LDL (r = 0.46 and 0.53, P < 0.01) and waist-to-hip ratio and total body fat (r = 0.41-0.44, all P < 0.05). Our results are consistent with the hypothesis that oxidative stress contributes to chronic leg vasoconstriction and reduced basal whole leg blood flow in estrogen-deficient postmenopausal women. This oxidative stress-related suppression of leg vascular conductance and blood flow may be linked in part to increased total and abdominal adiposity.

Comment on Point:Counterpoint “The muscle metaboreflex does/does not restore blood flow to contracting muscles”

The following letters are in response to the Point:Counterpoint series “The muscle metaboreflex does/does not restore blood flow to contracting muscles” that appeared in the January issue (vol. 100: 357–361, 2006; ). To the Editor : Although we

Muscle metaboreflex modulates the arterial baroreflex dynamic effects on peripheral vascular conductance in humans

We aimed to investigate the interaction between the arterial baroreflex and muscle metaboreflex [as reflected by alterations in the dynamic responses shown by leg blood flow (LBF: by the ultrasound Doppler method), leg vascular conductance (LVC), mean arterial blood pressure (MAP), and heart rate (HR)] in humans. In 12 healthy subjects (10 men and 2 women), who performed sustained 1-min handgrip exercise at 50% maximal voluntary contraction followed immediately by an imposed postexercise muscle ischemia (PEMI), 5-s periods of neck pressure (NP; 50 mmHg) or neck suction (NS; -60 mmHg) were used to evaluate carotid baroreflex function both at rest (Con) and during PEMI. First, the decreases in LVC and LBF and the augmentation of MAP elicited by NP were all greater during PEMI than in Con (DeltaLVC, -1.2 +/- 0.2 vs. -1.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, -97.3 +/- 11.2 vs. -177.0 +/- 21.8 ml/min; DeltaMAP, 6.7 +/- 1.2 vs. 11.5 +/- 1.4 mmHg, Con vs. PEMI; each P < 0.05). Second, in Con, NS significantly increased both LVC and LBF (DeltaLVC, 0.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, 46.6 +/- 9.8 ml/min; significant change from baseline: each P < 0.05), and, whereas during PEMI no significant increases in LVC and LBF occurred during NS itself (DeltaLVC, 0.2 +/- 0.1 ml.min(-1).mmHg(-1); DeltaLBF, 10.8 +/- 9.6 ml/min; each P > 0.05), a decrease was evident in each parameters at 5 s after the cessation of NS. Third, during PEMI, the decrease in MAP elicited by NS was smaller (DeltaMAP, -8.4 +/- 1.0 vs. -5.8 +/- 0.4 mmHg, Con vs. PEMI; P < 0.05), and it recovered to its initial level more quickly after NS (vs. Con). Finally, however, the HR responses to NS and NP were not different between PEMI and Con. These results suggest that during muscle metaboreflex activation in humans, the arterial baroreflex dynamic effect on peripheral vascular conductance is modulated, as exemplified by 1) an augmentation of the NP-induced LVC decrease, and 2) a loss of the NS-induced LVC increase.