Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo

2013 ◽  
Vol 305 (6) ◽  
pp. E745-E750 ◽  
Author(s):  
Eloise A. Bradley ◽  
Stephen M. Richards ◽  
Michelle A. Keske ◽  
Stephen Rattigan
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Femoral Artery ◽  
Metabolic Effects ◽  
Microvascular Blood Flow ◽  
Glucose Disposal ◽  
Artery Blood Flow ◽  
Femoral Artery Blood Flow ◽  
Microvascular Recruitment

Insulin stimulates microvascular recruitment in skeletal muscle, and this vascular action augments muscle glucose disposal by ∼40%. The aim of the current study was to determine the contribution of local nitric oxide synthase (NOS) to the vascular actions of insulin in muscle. Hooded Wistar rats were infused with the NOS inhibitor Nω-nitro-l-arginine methylester (l-NAME, 10 μM) retrogradely via the epigastric artery in one leg during a systemic hyperinsulinemic-euglycemic clamp (3 mU·min−1·kg−1 × 60 min) or saline infusion. Femoral artery blood flow, microvascular blood flow (assessed from 1-methylxanthine metabolism), and muscle glucose uptake (2-deoxyglucose uptake) were measured in both legs. Local l-NAME infusion did not have any systemic actions on blood pressure or heart rate. Local l-NAME blocked insulin-stimulated changes in femoral artery blood flow (84%, P < 0.05) and microvascular recruitment (98%, P < 0.05), and partially blocked insulin-mediated glucose uptake in muscle (reduced by 34%, P < 0.05). l-NAME alone did not have any metabolic effects in the hindleg. We conclude that insulin-mediated microvascular recruitment is dependent on local activation of NOS in muscle and that this action is important for insulin's metabolic actions.

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

2003 ◽  
Vol 285 (1) ◽  
pp. E123-E129 ◽  
Author(s):  
M. A. Vincent ◽  
E. J. Barrett ◽  
J. R. Lindner ◽  
M. G. Clark ◽  
S. Rattigan
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Glucose Disposal ◽  
Total Blood ◽  
Artery Flow ◽  
Microvascular Recruitment ◽  
Total Blood Flow

We examined the effects of inhibiting nitric oxide synthase with Nω-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU·min-1·kg-1) significantly increased hindlimb total blood flow (0.69 ± 0.02 to 1.22 ± 0.11 ml/min, P < 0.05), glucose uptake (0.27 ± 0.05 to 0.95 ± 0.08 μmol/min, P < 0.05), 1-MX uptake (5.0 ± 0.5 to 8.5 ± 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 ± 1.6 to 15.0 ± 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% ( P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound

2002 ◽  
Vol 282 (3) ◽  
pp. E714-E720 ◽  
Author(s):  
Dana Dawson ◽  
Michelle A. Vincent ◽  
Eugene J. Barrett ◽  
Sanjiv Kaul ◽  
Andrew Clark ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Femoral Artery ◽  
Artery Blood Flow ◽  
Contrast Enhanced Ultrasound ◽  
Contrast Enhanced ◽  
Adductor Muscles ◽  
Femoral Artery Blood Flow ◽  
Contrast Ultrasound

The purpose of this study was to noninvasively quantify the effects of insulin on capillary blood volume (capBV) and RBC velocity ( V RBC) in skeletal muscle in vivo with the use of contrast-enhanced ultrasound. We performed contrast ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h infusions of either insulin (3 or 40 mU · kg−1 · min−1) or saline. Saline-treated animals were also studied during contractile exercise. V RBC and capBV were calculated from the relation between pulsing interval and video intensity. Femoral artery blood flow, measured by a flow probe, increased with both contractile exercise and insulin. Contractile exercise increased capBV more than twofold and V RBC fivefold. Insulin also increased capBV more than twofold in a dose-dependent fashion but did not significantly alter V RBC. Saline infusion did not significantly alter capBV, V RBC, or femoral artery blood flow. We conclude that physiological changes in skeletal muscle capillary perfusion can be assessed in vivo with the use of contrast-enhanced ultrasound. Exercise increases both V RBC and capBV, whereas hyperinsulinemia selectively increases only capBV, which may enhance skeletal muscle glucose uptake.

scholarly journals Exercise training improves femoral artery blood flow responses to endothelium-dependent dilators in hypercholesterolemic pigs

2006 ◽  
Vol 290 (6) ◽  
pp. H2362-H2368 ◽  
Author(s):  
Christopher R. Woodman ◽  
David Ingram ◽  
John Bonagura ◽  
M. Harold Laughlin
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Artery Blood Flow ◽  
Femoral Arteries ◽  
Femoral Artery Blood Flow ◽  
Relaxation Responses ◽  
Oxide Synthase

We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex. Endothelium-dependent vasodilator responses were assessed in vivo by measuring changes in FABF after intra-arterial injections of ADP and bradykinin (BK). Endothelium-dependent and -independent relaxation was assessed in vitro by measuring relaxation responses to BK and sodium nitroprusside (SNP). FABF increased in response to ADP and BK in all groups. FABF responses to ADP and BK were not impaired by HF but were improved by Ex in HF pigs. BK- and SNP-induced relaxation of femoral artery rings was not altered by HF or Ex. To determine whether the mechanism(s) for vasorelaxation of femoral arteries was altered by HF or Ex, BK-induced relaxation was assessed in vitro in the absence or presence of NG-nitro-l-arginine methyl ester [l-NAME; to inhibit nitric oxide synthase (NOS)], indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. BK-induced relaxation was inhibited by l-NAME and l-NAME + Indo in all groups of femoral arteries. Ex increased the NOS-dependent component of endothelium-dependent relaxation in NF (not HF) arteries. Indo did not inhibit BK-induced relaxation. Collectively, these results indicate that hypercholesterolemia does not alter endothelial function in femoral arteries and that Ex training improves FABF responses to ADP and BK; however, the improvement cannot be attributed to enhanced endothelial function in HF femoral arteries. These data suggest that Ex-induced improvements in FABF in HF arteries are mediated by vascular adaptations in arteries/arterioles downstream from the femoral artery.

Kinetics of V̇o2 and femoral artery blood flow during heavy-intensity, knee-extension exercise

2005 ◽  
Vol 99 (2) ◽  
pp. 683-690 ◽  
Author(s):  
Nicole D. Paterson ◽  
John M. Kowalchuk ◽  
Donald H. Paterson
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Time Course ◽  
Slow Component ◽  
Knee Extension ◽  
Artery Blood Flow ◽  
Phase 2 ◽  
Femoral Artery Blood Flow ◽  
Knee Extension Exercise ◽  
Kinetics Of

It has been suggested that, during heavy-intensity exercise, O2 delivery may limit oxygen uptake (V̇o2) kinetics; however, there are limited data regarding the relationship of blood flow and V̇o2 kinetics for heavy-intensity exercise. The purpose was to determine the exercise on-transient time course of femoral artery blood flow (Q̇leg) in relation to V̇o2 during heavy-intensity, single-leg, knee-extension exercise. Five young subjects performed five to eight repeats of heavy-intensity exercise with measures of breath-by-breath pulmonary V̇o2 and Doppler ultrasound femoral artery mean blood velocity and vessel diameter. The phase 2 time frame for V̇o2 and Q̇leg was isolated and fit with a monoexponent to characterize the amplitude and time course of the responses. Amplitude of the phase 3 response was also determined. The phase 2 time constant for V̇o2 of 29.0 s and time constant for Q̇leg of 24.5 s were not different. The change (Δ) in V̇o2 response to the end of phase 2 of 0.317 l/min was accompanied by a ΔQ̇leg of 2.35 l/min, giving a ΔQ̇leg-to-ΔV̇o2 ratio of 7.4. A slow-component V̇o2 of 0.098 l/min was accompanied by a further Q̇leg increase of 0.72 l/min (ΔQ̇leg-to-ΔV̇o2 ratio = 7.3). Thus the time course of Q̇leg was similar to that of muscle V̇o2 (as measured by the phase 2 V̇o2 kinetics), and throughout the on-transient the amplitude of the Q̇leg increase achieved (or exceeded) the Q̇leg-to-V̇o2 ratio steady-state relationship (ratio ∼4.9). Additionally, the V̇o2 slow component was accompanied by a relatively large rise in Q̇leg, with the increased O2 delivery meeting the increased V̇o2. Thus, in heavy-intensity, single-leg, knee-extension exercise, the amplitude and kinetics of blood flow to the exercising limb appear to be closely linked to the V̇o2 kinetics.

Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans

1997 ◽  
Vol 83 (4) ◽  
pp. 1383-1388 ◽  
Author(s):  
G. Rådegran
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Coefficient Of Variation ◽  
Knee Extensor ◽  
Dynamic Exercise ◽  
Artery Blood Flow ◽  
Ultrasound Doppler ◽  
Femoral Artery Blood Flow ◽  
Human Limb ◽  
Exercise In Humans

Rådegran, G. Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J. Appl. Physiol.83(4): 1383–1388, 1997.—Ultrasound Doppler has been used to measure arterial inflow to a human limb during intermittent static contractions. The technique, however, has neither been thoroughly validated nor used during dynamic exercise. In this study, the inherent problems of the technique have been addressed, and the accuracy was improved by storing the velocity tracings continuously and calculating the flow in relation to the muscle contraction-relaxation phases. The femoral arterial diameter measurements were reproducible with a mean coefficient of variation within the subjects of 1.2 ± 0.2%. The diameter was the same whether the probe was fixed or repositioned at rest (10.8 ± 0.2 mm) or measured during dynamic exercise. The blood velocity was sampled over the width of the diameter and the parabolic velocity profile, since sampling in the center resulted in an overestimation by 22.6 ± 9.1% ( P< 0.02). The femoral arterial Doppler blood flow increased linearly ( r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 ⋅ load (W) + 1.446 l/min] and was correlated positively with simultaneous thermodilution venous outflow measurements ( r = 0.996, P < 0.001). The two techniques were linearly related (Doppler = thermodilution ⋅ 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient of variation of ∼6% for both methods.

Muscle Capillary and Femoral Artery Blood Flow Kinetics following the Onset of Exercise

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S196-S197
Author(s):  
Allison J. Harper ◽  
Leonardo F. Ferreira ◽  
Barbara J. Lutjemeier ◽  
Dana K. Townsend ◽  
Thomas J. Barstow
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Artery Blood Flow ◽  
Femoral Artery Blood Flow
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