Enhanced arteriolar α-adrenergic constriction impairs dilator responses and skeletal muscle perfusion in obese Zucker rats

2004 ◽  
Vol 97 (2) ◽  
pp. 764-772 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Zucker Rats ◽  
Metabolic Demand ◽  
Obese Zucker Rats ◽  
Isometric Twitch ◽  
Gastrocnemius Muscles

The present study tested the hypothesis that enhanced vascular α-adrenergic constriction in obese Zucker rats (OZR) impairs arteriolar dilation and perfusion of skeletal muscle at rest and with increased metabolic demand. In lean Zucker rats (LZR) and OZR, isolated gracilis arterioles were viewed via television microscopy, and the contralateral cremaster muscle or gastrocnemius muscle was prepared for study in situ. Gracilis and cremasteric arterioles were challenged with dilator stimuli under control conditions and after blockade of α-adrenoreceptors with prazosin, phentolamine, or yohimbine. Gastrocnemius muscles performed isometric twitch contractions of increasing frequency, and perfusion was continuously monitored. In OZR, dilator responses of arterioles to hypoxia (gracilis), wall shear rate (cremaster), acetylcholine, and iloprost (both) were impaired vs. LZR. Treatment with prazosin and phentolamine (and in cremasteric arterioles only, yohimbine) improved arteriolar reactivity to these stimuli in OZR, although responses remained impaired vs. LZR. Gastrocnemius muscle blood flow was reduced at rest in OZR; this was corrected with intravenous infusion of phentolamine or prazosin. At all contraction frequencies, blood flow was reduced in OZR vs. LZR; this was improved by infusion of phentolamine or prazosin at low-moderate metabolic demand only (1 and 3 Hz). At 5 Hz, adrenoreceptor blockade did not alter blood flow in OZR from levels in untreated rats. These results suggest that enhanced α-adrenergic constriction of arterioles of OZR contributes to impaired dilator responses and reduced muscle blood flow at rest and with mild-moderate (although not with large) elevations in metabolic demand.

Endothelial modulation of skeletal muscle blood flow andV˙o 2 during low- and high-intensity contractions

2002 ◽  
Vol 92 (2) ◽  
pp. 461-468 ◽  
Author(s):  
Cheryl E. King-VanVlack ◽  
J. D. Mewburn ◽  
C. K. Chapler ◽  
P. H. MacDonald
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Methyl Ester ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Tension Development ◽  
Anesthetized Dogs ◽  
Isometric Twitch ◽  
Oxide Synthase

In the present study, we determined whether endothelin (ET)-1 contributed to the observed reduction in muscle blood flow (Q˙) during contractions with nitric oxide synthase (NOS) inhibition and whether muscle O2 uptake (V˙o 2) would be affected by the decrease in muscle Q˙ with NOS inhibition at different contraction intensities. Muscle Q˙,V˙o 2, O2 extraction ratio (OER), and tension development (TD) were studied in the in situ gastrocnemius muscle preparation in anesthetized dogs. A decrease in the V˙o 2-to-TD ratio (V˙o 2/TD) was used as an indicator of O2 limitation. Three contraction protocols were used: 1) isometric twitch contractions at 2 twitches (tw)/s, 2) the same contractions at 4 tw/s, and 3) pretreatment with an ETA-receptor antagonist (BQ-123) before 2 tw/s contractions. The muscle was stimulated to contract, and measures were obtained at steady state (∼5–8 min). NOS inhibition ( N ω-nitro-l-arginine methyl ester) was then induced, and measures were repeated at 2, 5, 10, and 15 min. During 2 tw/s contractions, NOS inhibition reduced Q˙with and without ETA-receptor blockade. In both groups, OER increased in response to the fall in Q˙, with the result being no change in V˙o 2/TD. NOS inhibition also decreased Q˙ during 4 tw/s contractions, but OER did not increase, resulting in a reduction inV˙o 2/TD 5 and 15 min after N ω-nitro-l-arginine methyl ester. These data indicated that 1) a reciprocal increase in ET-1 during NOS inhibition does not influence active hyperemia in skeletal muscle, and 2) during 4 tw/s contractions, the ischemia with NOS inhibition was associated with either an O2 limitation or an alteration in the efficiency of muscle contractions.

scholarly journals Nonuniform effects of endurance exercise training on vasodilation in rat skeletal muscle

2005 ◽  
Vol 98 (2) ◽  
pp. 753-761 ◽  
Author(s):  
R. M. McAllister ◽  
J. L. Jasperse ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Second Order ◽  
Skeletal Muscle Blood Flow ◽  
Endurance Exercise Training

Endurance exercise training (Ex) has been shown to increase maximal skeletal muscle blood flow. The purpose of this study was to test the hypothesis that increased endothelium-dependent vasodilation is associated with the Ex-induced increase in muscle blood flow. Furthermore, we hypothesized that enhanced endothelium-dependent dilation is confined to vessels in high-oxidative muscles that are recruited during Ex. To test these hypotheses, sedentary (Sed) and rats that underwent Ex (30 m/min × 10% grade, 60 min/day, 5 days/wk, 8–12 wk) were studied using three experimental approaches. Training effectiveness was evidenced by increased citrate synthase activity in soleus and vastus lateralis (red section) muscles ( P < 0.05). Vasodilatory responses to the endothelium-dependent agent acetylcholine (ACh) in situ tended to be augmented by training in the red section of gastrocnemius muscle (RG; Sed: control, 0.69 ± 0.12; ACh, 1.25 ± 0.15; Ex: control, 0.86 ± 0.17; ACh, 1.76 ± 0.27 ml·min−1·100 g−1·mmHg−1; 0.05 < P < 0.10 for Ex vs. Sed during ACh). Responses to ACh in situ did not differ between Sed and Ex for either the soleus muscle or white section of gastrocnemius muscle (WG). Dilatory responses of second-order arterioles from the RG in vitro to flow (4–8 μl/min) and sodium nitroprusside (SNP; 10−7 through10−4 M), but not ACh, were augmented in Ex (vs. Sed; P < 0.05). Dilatory responses to ACh, flow, and SNP of arterioles from soleus and WG muscles did not differ between Sed and Ex. Content of the endothelial isoform of nitric oxide synthase (eNOS) was increased in second-order, fourth-order, and fifth-order arterioles from the RG of Ex; eNOS content was similar between Sed and Ex in vessels from the soleus and WG muscles. These findings indicate that Ex induces endothelial adaptations in fast-twitch, oxidative, glycolytic skeletal muscle. These adaptations may contribute to enhanced skeletal muscle blood flow in endurance-trained individuals.

Vascular adrenergic tone and structural narrowing constrain reactive hyperemia in skeletal muscle of obese Zucker rats

2006 ◽  
Vol 290 (5) ◽  
pp. H2066-H2074 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Vascular Resistance ◽  
Perfusion Pressure ◽  
Reactive Hyperemia ◽  
Zucker Rats ◽  
Cremaster Muscle ◽  
Metabolic Demand ◽  
Obese Zucker Rats

Previous studies have demonstrated that skeletal muscle perfusion is impaired in obese Zucker rats (OZR) under control conditions and with elevated metabolic demand versus responses in lean Zucker rats (LZR). To further our understanding of processes contributing to impaired perfusion, we determined whether hyperemic responses following periods of occlusion were altered in skeletal muscle of OZR versus LZR. In isolated hindlimbs, basal blood flow in OZR was less than in LZR, and total perfusion responses after 30, 90, and 180 s of occlusion were reduced. Treatment of animals with an antioxidant (polythethylene glycol-superoxide dismutase) had no effect on reactive hyperemia, although blockade of α-adrenoreceptors (α1 > α2) improved responses to 30 and 90 s of occlusion; responses to 180 s of occlusion were unaltered. Pump perfusion of a dilated distal hindlimb demonstrated that increased volume flow elicited a greater increase in perfusion pressure in OZR versus LZR, suggesting structural contributions to an increased vascular resistance. Responses were comparable for in situ cremaster muscle because reactive hyperemia following serial arteriolar occlusion was attenuated in OZR versus LZR, treatment with polythethylene glycol-superoxide dismutase was ineffective, and hyperemic responses were improved following inhibition of α-adrenoreceptors (α1 > α2). Treatment of cremaster muscle with adenosine (10−3 M) caused flow to increase to a level comparable to that following 180 s of occlusion in both strains, although this level was reduced in OZR versus LZR. These results suggest that increased adrenergic tone may constrain reactive hyperemia in OZR with brief occlusion, although structural increases in vascular resistance can contribute to constrained perfusion after longer periods of occlusion.

scholarly journals Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

2003 ◽  
Vol 285 (1) ◽  
pp. H104-H111 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Strain Curve ◽  
Zucker Rats ◽  
Metabolic Demand ◽  
Structural Alterations ◽  
Obese Zucker Rats ◽  
Skeletal Muscle Microcirculation ◽  
Acting In Concert

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

Impaired skeletal muscle perfusion in obese Zucker rats

2003 ◽  
Vol 285 (5) ◽  
pp. R1124-R1134 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Microvessel Density ◽  
Gastrocnemius Muscle ◽  
Oxidant Stress ◽  
Gracilis Muscle ◽  
Muscle Performance ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
The Impact

Skeletal muscle arterioles from obese Zucker rats (OZR) exhibit oxidant stress-based alterations in reactivity, enhanced α-adrenergic constriction, and reduced distensibility vs. microvessels of lean Zucker rats (LZR). The present study determined the impact of these alterations for perfusion and performance of in situ skeletal muscle during periods of elevated metabolic demand. During bouts of isometric tetanic contractions, fatigue of in situ gastrocnemius muscle of OZR was increased vs. LZR; this was associated with impaired active hyperemia. In OZR, vasoactive responses of skeletal muscle arterioles from the contralateral gracilis muscle were impaired, due in part to elevated oxidant tone; reactivity was improved after treatment with polyethylene glycol-superoxide dismutase (PEGSOD). Arterioles of OZR also exhibited increased α-adrenergic sensitivity, which was abolished by treatment with phentolamine (10-5 M). Intravenous infusion of phentolamine (10 mg/kg) or PEG-SOD (2,000 U/kg) in OZR altered neither fatigue rates nor active hyperemia from untreated levels; however, combined infusion improved performance and hyperemia, although not to levels in LZR. Microvessel density in the contralateral gastrocnemius muscle, determined via histological analyses, was reduced by ∼25% in OZR vs. LZR, while individual arterioles from the contralateral gracilis muscle demonstrated reduced distensibility. These data suggest that altered arteriolar reactivity contributes to reduced muscle performance and active hyperemia in OZR. Further, despite pharmacological improvements in arteriolar reactivity, reduced skeletal muscle microvessel density and arteriolar distensibility also contribute substantially to reduced active hyperemia and potentially to impaired muscle performance.

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

1990 ◽  
Vol 69 (3) ◽  
pp. 830-836 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
A. T. Gray ◽  
P. D. Wagner ◽  
J. B. West ◽  
...  
Keyword(s):  
Blood Flow ◽  
Muscle Blood Flow ◽  
Hemoglobin Concentration ◽  
O2 Uptake ◽  
Isometric Twitch ◽  
O2 Delivery ◽  
Arterial Po2 ◽  
O2 Dissociation Curve ◽  
Total Hemoglobin Concentration

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)

Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium

2000 ◽  
Vol 78 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Dilson E Rassier ◽  
Brian R MacIntosh
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Repetitive Stimulation ◽  
Mammalian Skeletal Muscle ◽  
Optimal Length ◽  
Dantrolene Sodium ◽  
Length Dependence ◽  
Before And After ◽  
Isometric Twitch

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 ± 12, 51 ± 5, and 34 ± 9% (mean ± SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65±13, 53 ± 11, and 45 ± 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 ± 17, 26 ± 8, and 18 ± 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

scholarly journals Role of convective O2 delivery in determiningV˙o 2 on-kinetics in canine muscle contracting at peak V˙o 2

2000 ◽  
Vol 89 (4) ◽  
pp. 1293-1301 ◽  
Author(s):  
Bruno Grassi ◽  
Michael C. Hogan ◽  
Kevin M. Kelley ◽  
William G. Aschenbach ◽  
Jason J. Hamann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Muscle Fatigue ◽  
Oxidative Metabolism ◽  
Muscle Blood Flow ◽  
Content Difference ◽  
O2 Delivery ◽  
Gastrocnemius Muscles

A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl Physiol 85: 1394–1403, 1998) showed that convective O2 delivery to muscle did not limit O2 uptake (V˙o 2) on-kinetics during transitions from rest to contractions at ∼60% of peakV˙o 2. The present study aimed to determine whether this finding is also true for transitions involving contractions of higher metabolic intensities.V˙o 2 on-kinetics were determined in isolated canine gastrocnemius muscles in situ ( n = 5) during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions corresponding to the muscle peakV˙o 2. Two conditions were compared: 1) spontaneous adjustment of muscle blood flow (Q˙) (Control) and 2) pump-perfused Q˙, adjusted ∼15–30 s before contractions at a constant level corresponding to the steady-state value during contractions in Control (Fast O2 Delivery). In Fast O2 Delivery, adenosine was infused intra-arterially. Q˙ was measured continuously in the popliteal vein; arterial and popliteal venous O2 contents were measured at rest and at 5- to 7-s intervals during the transition. Muscle V˙o 2 was determined as Q˙times the arteriovenous blood O2 content difference. The time to reach 63% of the V˙o 2 difference between resting baseline and steady-state values during contractions was 24.9 ± 1.6 (SE) s in Control and 18.5 ± 1.8 s in Fast O2 Delivery ( P < 0.05). FasterV˙o 2 on-kinetics in Fast O2Delivery was associated with an ∼30% reduction in the calculated O2 deficit and with less muscle fatigue. During transitions involving contractions at peak V˙o 2, convective O2 delivery to muscle, together with an inertia of oxidative metabolism, contributes in determining theV˙o 2 on-kinetics.

scholarly journals Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome

2009 ◽  
Vol 296 (6) ◽  
pp. R1771-R1782 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
John M. Hollander ◽  
Robert W. Brock ◽  
Han-Gang Yu ◽  
Matthew A. Boegehold
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Vascular Reactivity ◽  
Oxidant Stress ◽  
Zucker Rats ◽  
Minimal Effect ◽  
Metabolic Demand ◽  
The Metabolic Syndrome ◽  
The Impact

Previous study suggests that with evolution of the metabolic syndrome, patterns of arteriolar reactivity are profoundly altered and may constrain functional hyperemia. This study investigated interactions between parameters of vascular reactivity at two levels of resistance arterioles in obese Zucker rats (OZR), translating these observations into perfusion regulation for in situ skeletal muscle. Dilation of isolated and in situ resistance arterioles from OZR to acetylcholine, arachidonic acid (AA), and hypoxia (isolated arterioles only) were blunted vs. lean Zucker rats (LZR), although dilation to adenosine was intact. Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) impaired dilation in both strains (OZR>LZR). Treatment of OZR arterioles with Tempol (superoxide dismutase mimetic) or SQ-29548 (prostaglandin H2/thromboxane A2 receptor antagonist) improved dilator reactivity under control conditions and with increased ILP, but had minimal effect with increased adrenergic tone. Arteriolar dilation to adenosine was well maintained in both strains under all conditions. For in situ cremasteric arterioles, muscle contraction-induced elevations in metabolic demand elicited arteriolar dilations and hyperemic responses that were blunted in OZR vs. LZR, although distal parallel arterioles were characterized by heterogeneous dilator and perfusion responses. α-Adrenoreceptor blockade improved outcomes at rest but had minimal effect with elevated metabolic demand. Treatment with Tempol or SQ-29548 had minimal impact at rest, but lessened distal arteriolar perfusion heterogeneity with increased metabolic demand. In blood-perfused gastrocnemius of OZR, perfusion was constrained primarily by adrenergic tone, while myogenic activation and endothelium-dependent dilation did not appear to contribute significantly to ischemia. These results of this novel, integrated approach suggest that adrenergic tone and metabolic dilation are robust determinants of bulk perfusion to skeletal muscle of OZR, while endothelial dysfunction may more strongly regulate perfusion distribution homogeneity via the impact of oxidant stress and AA metabolism.

Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement

1995 ◽  
Vol 79 (2) ◽  
pp. 638-647 ◽  
Author(s):  
R. C. Hickner ◽  
U. Ekelund ◽  
S. Mellander ◽  
U. Ungerstedt ◽  
J. Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Roller Pump ◽  
Perfusion Flow ◽  
Quantitative Validation ◽  
Nonlinear Fashion ◽  
Perfusion Flow Rate ◽  
Krebs Henseleit Buffer

A quantitative validation of the microdialysis ethanol technique was performed in cat gastrocnemius muscle. Six to eight microdialysis probes were inserted into the isolated muscle preparation and perfused (0.5–10.0 microliters/min) with Krebs-Henseleit buffer containing between 5 and 1,000 mmol/l ethanol. Skeletal muscle blood flow was held constant in the range of 4–99 ml.100 g-1.min-1 by a servo-controlled roller pump and was determined with the microdialysis ethanol technique as well as by timed collection of venous outflow. The ethanol concentration outflow-to-inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium) decreased in a nonlinear fashion when microdialysis perfusion flow rates of 0.5 and 1.0 microliter/min were employed. However, a linear decrease was found between 4 and approximately 45 ml.100 g-1.min-1 (r = -0.92 to -0.99). The lower outflow-to-inflow ratio was at 4 ml.100 g-1.min-1 (i.e., due to a low probe perfusion flow rate or a large dialysis membrane), the greater the sensitivity of the method was. It is concluded that this nonradioactive technique provides a simple and valid method for determining nutritive blood flow in skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document