No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats

2015 ◽  
Vol 308 (10) ◽  
pp. R862-R871 ◽  
Author(s):  
Yet Hoi Hong ◽  
Andrew C. Betik ◽  
Dino Premilovac ◽  
Renee M. Dwyer ◽  
Michelle A. Keske ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Femoral Artery ◽  
Systemic Blood Pressure ◽  
Sprague Dawley ◽  
Capillary Recruitment ◽  
Sprague Dawley Rats ◽  
Skeletal Muscle Glucose Uptake

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.

scholarly journals Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle

2018 ◽  
Vol 115 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Dino Premilovac ◽  
Emily Attrill ◽  
Stephen Rattigan ◽  
Stephen M Richards ◽  
Jeonga Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Skeletal Muscle Glucose Uptake

Abstract Aims Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin’s microvascular and metabolic actions in skeletal muscle. Methods and results Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals’ systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin’s effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake. Conclusions Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin’s microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil

1992 ◽  
Vol 263 (3) ◽  
pp. H945-H950 ◽  
Author(s):  
S. P. Sutera ◽  
K. Chang ◽  
J. Marvel ◽  
J. R. Williamson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Sciatic Nerve ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Citrate Buffer ◽  
Ocular Tissues ◽  
Arterial Blood ◽  
Transit Times ◽  
Sprague Dawley Rats

These studies were undertaken to investigate the relationship between regional hemodynamic and hemorheological changes in the microvasculature of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection of streptozotocin (55 mg/kg body wt). Control rats were injected with vehicle (sodium citrate buffer). A subgroup of diabetic rats was treated with an aldose reductase inhibitor (sorbinil) added to the diet in an amount to provide a daily dose of approximately 0.2 mmol.kg-1.day-1. Three weeks later all animals were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg injected intraperitoneally) for assessment of blood flow (by injection of 15 microns microspheres) and regional hematocrit (determined by isotope-dilution techniques using 51Cr-labeled red blood cells and 125I-labeled bovine serum albumin) in selected tissues. The hematocrit in arterial blood samples was identical (approximately 46%) in controls and in diabetics. Regional hematocrits were much lower than arterial hematocrits in control rats and ranged from approximately 20% in ocular tissues, sciatic nerve, diaphragm, and skin to approximately 30% in brain, skeletal muscle, heart, and fat. Hematocrits of diabetic rats were markedly increased in ocular tissues, sciatic nerve, and skin but not in brain, heart, or skeletal muscle. These increases in regional hematocrit were associated with increases in blood flow and were largely prevented by sorbinil. Diabetes induced significant decreases in the mean transit times for whole blood and erythrocytes in all tissues examined except brain, retina, and skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Large and Uneven Bites in End-to-End Anastomosis of the Rat Femoral Artery

2020 ◽  
Vol 36 (07) ◽  
pp. 486-493
Author(s):  
Yuan Dian Zheng ◽  
Celine F. Nicolas ◽  
John J. Corvi ◽  
Joey S. Kurtzman ◽  
Katherine H. Park ◽  
...  
Keyword(s):  
Blood Flow ◽  
Skill Acquisition ◽  
Femoral Artery ◽  
Sprague Dawley ◽  
Flow Measurements ◽  
Bite Size ◽  
Sprague Dawley Rats ◽  
Vessel Patency ◽  
End To End ◽  
Blood Flow Measurements

Abstract Background Successful microvascular anastomosis depends on sutures that adequately oppose both cut vessel edges. Trainees tend to take oversized or uneven bite. To improve early microsurgical skill acquisition using the rat, this study tests the belief that such bites compromise early patency by applying exaggerated bites to end-to-end arterial anastomoses. Methods Twelve Sprague–Dawley rats were randomly assigned to one of the four bite techniques to be applied to both femoral arteries (mean diameter, 0.8 mm). Large (L) and standard (S) bites measured 1.0 and 0.2 mm from the edge, respectively. Eight simple interrupted anastomoses were performed per bite technique, each labeled according to every proximal end bite size, followed by every distal end bite size: LL, LS, SL, and SS. Anastomosis time and blood flow rates were recorded and analyzed statistically. After sacrifice 5 days postoperation, anastomosis sections of each technique were examined histologically. Results All 24 anastomoses (100%) maintained patency for 5 days. There was no statistical difference between all postoperative blood flow measurements at any given time. Anastomosis times using LL, LS, SL, and SS bite techniques were 41.6, 33.2, 34.8, and 25.5 minutes, respectively. Anastomosis time for the traditional bite technique (SS) was significantly shorter than all other bite techniques (p < 0.05). Histological examination of the harvested segments from each group revealed similar pathophysiological features. Conclusion Oversized bites (1 mm), placed symmetrically and asymmetrically across the anastomosis, do not affect early patency in the rat femoral artery. A reduced reliance on conventional guidelines for suture bites appears acceptable during microarterial anastomoses if the goal is vessel patency. However, we believe clinical competence involves the ability to place small, even bites consistently and uniformly. During microsurgical training, the occasional large bite need not be replaced; however, the trainee should be encouraged to take standard bites.

Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat

2010 ◽  
Vol 108 (5) ◽  
pp. 1275-1283 ◽  
Author(s):  
T. L. Merry ◽  
R. M. Dywer ◽  
E. A. Bradley ◽  
S. Rattigan ◽  
G. K. McConell
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Moderate Intensity ◽  
Ampk Signaling ◽  
Epigastric Artery ◽  
Hindlimb Muscle ◽  
Skeletal Muscle Glucose Uptake ◽  
Amp Activated Protein Kinase

There is evidence that reactive oxygen species (ROS) contribute to the regulation of skeletal muscle glucose uptake during highly fatiguing ex vivo contraction conditions via AMP-activated protein kinase (AMPK). In this study we investigated the role of ROS in the regulation of glucose uptake and AMPK signaling during low-moderate intensity in situ hindlimb muscle contractions in rats, which is a more physiological protocol and preparation. Male hooded Wistar rats were anesthetized, and then N-acetylcysteine (NAC) was infused into the epigastric artery (125 mg·kg−1·h−1) of one hindlimb (contracted leg) for 15 min before this leg was electrically stimulated (0.1-ms impulse at 2 Hz and 35 V) to contract at a low-moderate intensity for 15 min. The contralateral leg did not receive stimulation or local NAC infusion (rest leg). NAC infusion increased ( P < 0.05) plasma cysteine and cystine (by ∼360- and 1.4-fold, respectively) and muscle cysteine (by 1.5-fold, P = 0.001). Although contraction did not significantly alter muscle tyrosine nitration, reduced (GSH) or oxidized glutathione (GSSG) content, S-glutathionylation of protein bands at ∼250 and 150 kDa was increased ( P < 0.05) ∼1.7-fold by contraction, and this increase was prevented by NAC. Contraction increased ( P < 0.05) skeletal muscle glucose uptake 20-fold, AMPK phosphorylation 6-fold, ACCβ phosphorylation 10-fold, and p38 MAPK phosphorylation 60-fold, and the muscle fatigued by ∼30% during contraction and NAC infusion had no significant effect on any of these responses. This was despite NAC preventing increases in S-glutathionylation with contraction. In conclusion, unlike during highly fatiguing ex vivo contractions, local NAC infusion during in situ low-moderate intensity hindlimb contractions in rats, a more physiological preparation, does not attenuate increases in skeletal muscle glucose uptake or AMPK signaling.

Increased skeletal muscle capillarization enhances insulin sensitivity

2014 ◽  
Vol 307 (12) ◽  
pp. E1105-E1116 ◽  
Author(s):  
Thorbjorn Akerstrom ◽  
Lasse Laub ◽  
Kenneth Vedel ◽  
Christian Lehn Brand ◽  
Bente Klarlund Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Blood Stream ◽  
Whole Body ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats ( n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[3H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[3H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

Effect of hindlimb unweighting on anaerobic metabolism in rat skeletal muscle

1992 ◽  
Vol 72 (4) ◽  
pp. 1304-1310 ◽  
Author(s):  
D. R. Marsh ◽  
C. B. Campbell ◽  
L. L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Anaerobic Metabolism ◽  
Sprague Dawley ◽  
Tension Development ◽  
Atp Production ◽  
Hindlimb Unweighting ◽  
Glycolytic Activity ◽  
Sprague Dawley Rats ◽  
Anaerobic Environment

Female Sprague-Dawley rats (250 g) were hindlimb suspended for 14 days, and the effects of hindlimb unweighting (HU) on skeletal muscle anaerobic metabolism were investigated and compared with nonsuspended controls (C). Soleus (SOL), plantaris (PL), and red and white portions of the gastrocnemius (RG, WG) were sampled from resting and stimulated limbs. Muscle atrophy after HU was 46% in SOL, 22% in PL, and 24% in the gastrocnemius compared with nonsuspended C animals. The muscles innervated by the sciatic nerve were stimulated to contract with an occluded circulation for 60 s with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1.0 Hz. Peak tension development by the gastrocnemius-PL-SOL muscle group was similar in HU and C animals (13.0 +/- 1.2, 12.2 +/- 0.8 N/g wet muscle). Occlusion of the circulation before stimulation created a predominantly anaerobic environment, and in situ glycogenolysis and glycolysis were estimated from accumulations of glycolytic intermediates. Total glycogenolysis and glycolysis were higher in the RG muscle of HU animals (74.6 +/- 3.3, 58.1 +/- 1.1) relative to C (57.1 +/- 4.6, 46.1 +/- 2.9 mumol glucosyl units/g dry muscle). Consequently, total anaerobic ATP production was also increased (HU, 251.3 +/- 1.1; C, 204.6 +/- 8.9 mumol ATP/g dry muscle). Total ATP production, glycogenolysis, and glycolysis were unaffected by HU in SOL, PL, and WG muscles. The enhanced glycolytic activity in RG after HU may be attributed to a shift in the metabolic profile from oxidative to glycolytic in the fast oxidative-glycolytic fiber population.

Reduced renal vascular response to nerve stimulation and norepinephrine in DOCA–salt hypertensive rats

1983 ◽  
Vol 61 (5) ◽  
pp. 464-471 ◽  
Author(s):  
R. L. Kline
Keyword(s):  
Blood Flow ◽  
Nerve Stimulation ◽  
Barium Chloride ◽  
Sprague Dawley ◽  
Control Groups ◽  
Renal Vasculature ◽  
Vascular Responses ◽  
Sprague Dawley Rats ◽  
Renal Vascular

Vascular responses to nerve stimulation and norepinephrine (NE) administration were studied in kidneys perfused in situ at constant flow in uninephrectomized Sprague–Dawley rats made hypertensive by 5–6 weeks of deoxycorticosterone acetate (DOCA) – salt treatment. One- and two-kidney normotensive rats were used as controls. Renal blood flow on a weight basis did not differ significantly between the two control groups. Kidneys of DOCA–salt rats were nearly twice the size of those in one-kidney controls, but blood flow was only half that of controls when perfusion pressure was set at 100 mmHg (1 mmHg = 133.322 Pa). There were no differences in renal vascular responses to nerve stimulation (2–8 Hz) or NE (10–50 ng, ia) between the two control groups; however, in the DOCA–salt rats, responses to nerve stimulation were decreased by 71–87%, while those to NE were decreased by 35–40%. Similar reductions in the response to barium chloride were seen. NE concentration in the perfused kidneys averaged 183 ± 11, 104 ± 16, and 37 ± 3 ng/g in the two-kidney, one-kidney, and DOCA–salt groups, respectively. The decrease in NE concentration in DOCA–salt kidneys was greater than could be accounted for by changes in renal mass alone. In another group of uninephrectomized rats, renal vascular resistance was increased to levels seen in DOCA–salt kidneys by iv infusion of NE. Under these conditions, responses to bolus injections of NE (50 ng) were decreased by 38%. Taken together, the results suggest that renal vascular responses to nerve stimulation in DOCA–salt kidneys are markedly reduced because of (i) a reduced amount of NE available for release, and (ii) a decreased responsiveness of the renal vasculature to NE. The latter response, which may extend to other vasoconstrictors as well, is opposite to what has been shown frequently in isolated, perfused kidneys, and may be explained by the presence of elevated renal vascular tone in DOCA–salt kidneys perfused in situ.

Effects of insulin on regional blood flow and glucose uptake in Wistar and Sprague-Dawley rats

Metabolism ◽  
2001 ◽  
Vol 50 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Nathalie Gaudreault ◽  
Marta Santuré ◽  
Maryse Pitre ◽  
André Nadeau ◽  
André Marette ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Regional Blood Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Prior exercise training increases collateral-dependent blood flow in rats after acute femoral artery occlusion

2000 ◽  
Vol 279 (4) ◽  
pp. H1890-H1897 ◽  
Author(s):  
H. T. Yang ◽  
M. Harold Laughlin ◽  
Ronald L. Terjung
Keyword(s):  
Blood Flow ◽  
Exercise Training ◽  
Femoral Artery ◽  
Vascular Occlusion ◽  
Artery Occlusion ◽  
Acute Onset ◽  
Treadmill Running ◽  
Prior Training ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

We evaluated whether prior training would improve collateral blood flow (BF) to the calf muscles after acute-onset occlusion of the femoral artery. Exercise training was performed in the absence of any vascular occlusion. Adult male Sprague-Dawley rats (∼325 g) were kept sedentary ( n = 14), limited to cage activity, or exercise trained ( n = 14) for 6 wk by treadmill running. Early in the day of measurement, animals were surgically prepared for BF determination, and the femoral arteries were occluded bilaterally. Four to five hours later, collateral BF was determined twice during treadmill running with the use of 141Ce and85Sr microspheres: first, at a demanding speed and, second, after a brief rest and at a higher speed. The absence of any further increase in BF at the higher speed indicated that maximal collateral BF was measured. Prior training increased calf muscle BF by ∼70% compared with sedentary animals; however, absolute BF remained below values previously observed in animals with a well-developed collateral vascular tree. Thus prior training appeared to optimize the use of the existing collateral circuit. This implies that altered vasoresponsiveness induced in normal nonoccluded vessels with exercise training serves to improve collateral BF to the periphery.

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