Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.

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Differential effects of anesthetics on in vivo skeletal muscle contractile function in the mouse

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.1.332 ◽

1996 ◽

Vol 80 (1) ◽

pp. 332-340 ◽

Cited By ~ 34

Author(s):

C. P. Ingalls ◽

G. L. Warren ◽

D. A. Lowe ◽

D. B. Boorstein ◽

R. B. Armstrong

Keyword(s):

Skeletal Muscle ◽

Contractile Function ◽

Average Power ◽

Eccentric Contraction ◽

Peak Torque ◽

High Dose ◽

Skeletal Muscle Function ◽

Contractile Responses ◽

Time Integral

The purpose of this study was to evaluate the effects of four anesthetic regimens on in vivo contractile function of mouse ankle dorsiflexor muscles. The torque-frequency and torque-velocity relationships were determined for the following anesthetics: fentanyl-droperidol and diazepam (F-d/d); ketamine and xylazine (K/x); pentobarbital sodium (Ps); and methoxyflurane (Mf). Mf, Ps, and F-d/d regimens resulted in comparable contractile responses at low doses, whereas K/x produced a relative depression in isometric contractile function as shown by a decrease in the torque-time integral at the 300-Hz stimulation frequency (-13.9%; P < 0.05). Moreover, K/x caused a shift to the left in the torque-frequency curve as indicated by increases in torque-time integrals at 25 and 50 Hz. Both Ps and F-d/d regimens exhibited dose-dependent effects during the isovelocity contractions. Ps significantly reduced work (-28.7%) and average power (-28.9%) at 800 degrees/s at the high dose. In contrast, F-d/d anesthesia resulted in increases in peak torque (16-20%) and work (15-18%) output at all eccentric contraction velocities at the high dose, whereas average power was increased only at -800 (17%) and -1,000 degrees/s (17%). In conclusion, commonly used anesthetic regimens can affect the contractile response in vivo; K/x and Ps yield smaller torque outputs, whereas Mf and F-d/d consistently produce larger contractile responses. Mf and F-d/d are recommended for use in studying skeletal muscle function in mice in vivo.

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Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.6.e1061 ◽

1996 ◽

Vol 271 (6) ◽

pp. E1061-E1066 ◽

Cited By ~ 15

Author(s):

D. Meynial-Denis ◽

M. Mignon ◽

A. Miri ◽

J. Imbert ◽

E. Aurousseau ◽

...

Keyword(s):

Skeletal Muscle ◽

Glutamine Synthetase ◽

Skeletal Muscles ◽

Female Rats ◽

Mrna Levels ◽

Aged Rats ◽

Adult Rats ◽

Adult Age ◽

Slow Twitch ◽

Fast Twitch

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

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Hippocampal glutamine synthetase: insensitivity to glucocorticoids and stress

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.258.5.e894 ◽

1990 ◽

Vol 258 (5) ◽

pp. E894-E897 ◽

Cited By ~ 1

Author(s):

G. C. Tombaugh ◽

R. M. Sapolsky

Keyword(s):

Skeletal Muscle ◽

Central Nervous System ◽

Nervous System ◽

Glutamine Synthetase ◽

Glutamate Metabolism ◽

Glutamatergic Synapses ◽

Adult Rats ◽

Glucocorticoid Induction ◽

The Central Nervous System ◽

The Brain

Glucocorticoids enhance the neurotoxic potential of several insults to the rat hippocampus that involve overactivation of glutamatergic synapses. These hormones also stimulate the synthesis of glutamine synthetase (GS) in peripheral tissue. Because this enzyme helps regulate glutamate metabolism in the central nervous system, glucocorticoid induction of GS in the brain may underlie the observed synergy. We have measured GS activity in the hippocampus and skeletal muscle (plantaris) of adult rats after bilateral adrenalectomy (ADX), corticosterone (Cort) replacement, or stress. No significant changes in GS were observed in hippocampal tissue, whereas muscle GS was significantly elevated after Cort treatment or stress and was reduced after ADX. These results suggest that Cort-induced shifts in GS activity probably do not explain Cort neurotoxicity, although the stress-induced rise in muscle GS may be relevant to certain types of myopathy.

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Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

Frontiers in Physiology ◽

10.3389/fphys.2021.726354 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ekaterina K. Selivanova ◽

Dina K. Gaynullina ◽

Olga S. Tarasova

Keyword(s):

Skeletal Muscle ◽

Kinase Inhibitors ◽

Isometric Force ◽

Rho Kinase ◽

Integrin Αvβ3 ◽

Acute Effects ◽

Rat Skeletal Muscle ◽

Subsequent Decrease ◽

Adrenoceptor Agonist ◽

Male Wistar Rats

Aim: Hyperthyroidism is associated with a decreased peripheral vascular resistance, which could be caused by the vasodilator genomic or non-genomic effects of thyroid hormones (TH). Non-genomic, or acute, effects develop within several minutes and involve a wide tissue-specific spectrum of molecular pathways poorly studied in vasculature. We aimed to investigate the mechanisms of acute effects of TH on rat skeletal muscle arteries.Methods: Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting).Results: Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α1-adrenoceptor agonist methoxamine. The effect of T4 was more prominent than T3 and not affected by iopanoic acid, an inhibitor of deiodinase 2. Endothelium denudation abolished the effect of T3, but not T4. Integrin αvβ3 inhibitor tetrac abolished the effect of T4 in endothelium-denuded arteries. T4 weakened methoxamine-induced elevation of phospho-MLC2 (Ser19) content in arterial samples. The effect of T4 in endothelium-denuded arteries was abolished by inhibiting ERK1/2 activation with U0126 as well as by ILK inhibitor Cpd22 but persisted in the presence of Src- or Rho-kinase inhibitors (PP2 and Y27632, respectively).Conclusion: Acute non-genomic relaxation of sural arteries induced by T3 is endothelium-dependent and that induced by T4 is endothelium-independent. The effect of T4 on α1-adrenergic contraction is stronger compared to T3 and involves the suppression of extracellular matrix signaling via integrin αvβ3, ERK1/2 and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.

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Effect of electromagnetic field GSM on contractile responses of fast‐twitch intact skeletal muscle fibers

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.1051.15 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Wiam Ramadan ◽

Hanane Akhdar ◽

Fatima Jebai ◽

Yolla Makhour ◽

Dana Zeyneddine ◽

...

Keyword(s):

Skeletal Muscle ◽

Electromagnetic Field ◽

Muscle Fibers ◽

Contractile Responses ◽

Skeletal Muscle Fibers ◽

Fast Twitch

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The influence of pH on the effects of organic anions in frog skeletal muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y77-155 ◽

1977 ◽

Vol 55 (5) ◽

pp. 1122-1134 ◽

Cited By ~ 1

Author(s):

J. G. Foulks ◽

Florence A. Perry ◽

P. Tsang

Keyword(s):

Skeletal Muscle ◽

Divalent Cations ◽

Organic Anions ◽

Frog Skeletal Muscle ◽

Depressant Effect ◽

Contractile Responses ◽

Neutral Ph ◽

Acid Ph ◽

Depressant Action ◽

Carboxylate Anions

The depressant effect of acidity on twitches and K contractures in frog skeletal muscle was greatly accentuated in the presence of organic anions, particularly anions such as butyrate, which also reduced these responses at neutral pH. Conversely, alkaline pH antagonized the depression of contractile responses by butyrate. Most of the effects of acid pH were rapid in onset and were accomplished without any change in membrane resting or action potentials, although depolarization developed in the presence of carboxylate anions when pH was reduced below 6.0. Simultaneous variation in pH and butyrate concentration showed that the undissociated acid exerted a prominent depressant effect only when its concentration reached 1–10 mM, and that the marked depressant action of butyrate at neutral pH was produced primarily by the dissociated anion. Similar experiments showed that the dissociated anion also was largely responsible for the enhanced depolarizing effect of acidity in media containing carboxylates. Acid-induced depolarization was not facilitated in media containing methane sulfonate, but in spite of its low pKa, this anion also increased the sensitivity of contractile responses to the depressant effects of acidity. Hence, the accentuation of the effects of organic anions by acid pH must be exerted on the sequence of membrane events which link excitation and contraction. The effect of acidity was greater when longer apolar hydrocarbon chains were attached to the anionic group for both the carboxylate and the sulfonate series of ions. These depressant effects may be produced by interference with the membrane-stabilizing actions of divalent cations, and may involve increased membrane fluidity.

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The effect of high-fat–high-fructose diet on skeletal muscle mitochondrial energetics in adult rats

European Journal of Nutrition ◽

10.1007/s00394-014-0699-7 ◽

2014 ◽

Vol 54 (2) ◽

pp. 183-192 ◽

Cited By ~ 18

Author(s):

Raffaella Crescenzo ◽

Francesca Bianco ◽

Paola Coppola ◽

Arianna Mazzoli ◽

Luisa Cigliano ◽

...

Keyword(s):

Skeletal Muscle ◽

High Fat ◽

Adult Rats ◽

High Fructose Diet ◽

High Fructose

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Ca2+sensitization and PKC contribute to exercise training-enhanced contractility in porcine collateral-dependent coronary arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00957.2010 ◽

2011 ◽

Vol 300 (4) ◽

pp. H1201-H1209 ◽

Cited By ~ 9

Author(s):

Juan Carlos Robles ◽

Michael Sturek ◽

Janet L. Parker ◽

Cristine L. Heaps

Keyword(s):

Exercise Training ◽

Coronary Arteries ◽

Contractile Function ◽

Rho Kinase ◽

Luminal Diameter ◽

Contractile Responses ◽

Endothelin 1 ◽

Increased Sensitivity ◽

Oxide Synthase ◽

Response Exercise

Exercise training enhances endothelium-dependent coronary vasodilatation, improving perfusion and contractile function of collateral-dependent myocardium. Paradoxically, studies from our laboratory have revealed increased Ca2+-dependent basal active tone in collateral-dependent arteries of exercise-trained pigs. In this study, we tested the hypothesis that exercise training enhances agonist-mediated contractile responses of collateral-dependent arteries by promoting Ca2+sensitization. Ameroid constrictors were surgically placed around the proximal left circumflex coronary (LCX) artery of female Yucatan miniature pigs. Eight weeks postoperatively, pigs were randomized into sedentary (pen confined) or exercise-training (treadmill run; 5 days/wk; 14 wk) groups. Arteries (∼150 μm luminal diameter) were isolated from the collateral-dependent and nonoccluded (left anterior descending artery supplied) myocardial regions, and measures of contractile tension or simultaneous tension and intracellular free Ca2+concentration levels (fura-2) were completed. Exercise training enhanced contractile responses to endothelin-1 in collateral-dependent compared with nonoccluded arteries, an effect that was more pronounced in the presence of nitric oxide synthase inhibition ( Nω-nitro-l-arginine methyl ester; 100 μM). Contractile responses to endothelin-1 were not altered by coronary occlusion alone. Exercise training produced increased tension at comparable levels of intracellular free Ca2+concentration in collateral-dependent compared with nonoccluded arteries, indicative of exercise training-enhanced Ca2+sensitization. Inhibition of PKC (calphostin C; 1 μM), but not Rho-kinase (Y-27632, 10 μM; or hydroxyfasudil, 30 μM), abolished the training-enhanced endothelin-1-mediated contractile response. Exercise training also increased sensitivity to the PKC activator phorbol 12,13-dibutyrate in collateral-dependent compared with nonoccluded arteries. Taken together, these data reveal that exercise training enhances endothelin-1-mediated contractile responses in collateral-dependent coronary arteries likely via increased PKC-mediated Ca2+sensitization.

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Leucine-Rich Diet Modulates the Metabolomic and Proteomic Profile of Skeletal Muscle during Cancer Cachexia

Cancers ◽

10.3390/cancers12071880 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1880 ◽

Cited By ~ 1

Author(s):

Bread Cruz ◽

André Oliveira ◽

Lais Rosa Viana ◽

Leisa Lopes-Aguiar ◽

Rafael Canevarolo ◽

...

Keyword(s):

Skeletal Muscle ◽

Cancer Cachexia ◽

Energy Generation ◽

In Vitro Assays ◽

Proteomic Profile ◽

Adult Rats ◽

Vitro Assay ◽

Tumour Bearing

Background: Cancer-cachexia induces a variety of metabolic disorders, including skeletal muscle imbalance. Alternative therapy, as nutritional supplementation with leucine, shows a modulatory effect over tumour damage in vivo and in vitro. Method: Adult rats distributed into Control (C), Walker tumour-bearing (W), control fed a leucine-rich diet (L), and tumour-bearing fed a leucine-rich diet (WL) groups had the gastrocnemius muscle metabolomic and proteomic assays performed in parallel to in vitro assays. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. In vitro assay showed that cell proliferation, mitochondria number and oxygen consumption were higher under leucine effect than the tumour influence. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia.

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