scholarly journals Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

2018 ◽  
Vol 17 (4) ◽  
pp. 23-32
Author(s):  
D. K. Gaynullina ◽  
E. K. Selivanova ◽  
A. P. Sharova ◽  
O. S. Tarasova

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.

2018 ◽  
Vol 84 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Dina K. Gaynullina ◽  
Svetlana I. Sofronova ◽  
Anastasia A. Shvetsova ◽  
Ekaterina K. Selivanova ◽  
Anna P. Sharova ◽  
...  

2016 ◽  
Vol 310 (3) ◽  
pp. E213-E224 ◽  
Author(s):  
Marie Le Guen ◽  
Valérie Chaté ◽  
Isabelle Hininger-Favier ◽  
Brigitte Laillet ◽  
Béatrice Morio ◽  
...  

Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions ( P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Km for ADP ( P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group ( P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group ( P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina K. Selivanova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova

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.


2020 ◽  
Author(s):  
William N. Sanchez ◽  
Jose A. Pochapski ◽  
Leticia F. Jessen ◽  
Marek Ellenberger ◽  
Rainer K. Schwarting ◽  
...  

AbstractBackground and PurposeCurrently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats.Experimental ApproachHere we tested whether administration of 2.5 mg·kg−1 diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg·kg−1 cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity.Key ResultsCocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%.Conclusions and implicationThese results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam.What is already knownDiazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine.What this study addsDiazepam attenuated the increase in phasic dopamine release caused by cocaine.Diazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity.Clinical significanceThis study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction.


2020 ◽  
pp. 35-40
Author(s):  
И. В. Саматошенков

Цель - оценить эффективность реваскуляризации икроножной мышцы крысы в условиях прямой и опосредованной мононуклеарными клетками крови пуповины человека (МККП) доставки в область ишемии рекомбинантного гена ангиогенина (Ang) человека при помощи аденовирусного вектора 5-го серотипа (Ad5). Материал и методы. Исследования проведены на 30 крысах линии Wistar. Через 14 сут после иссечения фрагмента бедренной артерии животным инъецировали в ишемизированную икроножную мышцу генетическую конструкцию (группа Ad5-Ang, n=15). Крысам другой группы (МККП+Ad5-Ang, n=15) в тот же срок трансген доставляли в мышцу при помощи МККП. В группе контроля животным (n=15) вводили в мышцу 0,9 % NaCl в тех же условиях. Через 14 и 28 сут в области ишемии оценивали отношение капилляры/мышечные волокна, количество мышечных волокон и количество мышечных волокон с центральным расположением ядер (МЦЯ). Капилляры идентифицировали по локализации эндотелиальных клеток, выявляемых при помощи иммуногистохимической реакции с антителами против CD31. Результаты. На 14-е сутки после введения МККП+Ad5-Ang показатель отношения количества капилляров к количеству мышечных волокон в области ишемии увеличивается на 57 % (p<0,05). На 28-е сутки в группе МККП+Ad5-Ang и в группе Ad5-Ang значимые различия по данному показателю при сравнении с контрольной группой не выявлены. Количество мышечных волокон на 14-е сутки в группе Ad5-Ang не изменяется, а в группе МККП+Ad5-Ang - уменьшается на 58,4 % (p<0,05). К 28-м суткам этот показатель в группе МККП+Ad5-Ang уменьшается на 95,9 % (p<0,05), а в группе Ad5-Ang - на 197,8 % (p<0,05). Количество МЦЯ существенно увеличивается в обеих экспериментальных группах с применением генетических конструкций на 14-е сутки. Выводы. Введение рекомбинантного гена Ang в область ишемии скелетной мышцы или его доставка в эту область при помощи мононуклеарных клеток крови пуповины стимулирует ангиогенез и постишемическую регенерацию мышечных волокон. Objective - to evaluate the effectiveness of revascularization of the rat gastrocnemius muscle following direct and human umbilical cord blood mononuclear cells (MNCs)-mediated delivery of human recombinant angiogenin (Ang) gene to the ischemic area using adenovirus serotype 5 vector (Ad5). Materials and methods. The study was carried out on 30 Wistar rats. Fourteen days after the excision of the femoral artery fragment, the genetic construct was injected into the animals’ ischemic gastrocnemius muscle (AD5-Ang group, n=15). In the other group (mccp+Ad5-Ang, n=15), the transgene was delivered to the muscle with the help of MNCs within the same time limit. In the control group (n=15) 0,9 % NaCl was injected into the muscle of animals under the same conditions. Fourteen and twenty-eight days after the injection, the ratio of capillaries/muscle fibers, the number of muscle fibers and the number of muscle fibers with a central location of nuclei (MCN) were evaluated in the ischemic area. Capillaries were identified by localization of endothelial cells detected by immunohistochemical reaction with antibodies against CD31. Results. On the 14th day after administration of MNCs+Ad5Ang, the ratio of capillaries to the number of muscle fibers in the ischemic area increased by 57 % (p<0,05). On the 28th day in the MNCs+Ad5-Ang group and in the Ad5-Ang group, no significant differences in this indicator were found compared with the control group. The number of muscle fibers on the 14 day in the Ad5-Ang group did not change, and in the MNCs+Ad5-Ang group, it decreased by 58,4 % (p<0,05). By the 28th day, this indicator in the MNCs+Ad5-Ang group decreased by 95,9 % (p<0,05), and in the Ad5-Ang group - by 197,8 % (p<0,05). The number of MCN on the 14 day significantly increased in both experimental groups, in which the genetic constructs were used. Conclusion. The introduction of recombinant ang gene into the area of skeletal muscle ischemia or its delivery to this area with the help of MCNs stimulates angiogenesis and post-ischemic regeneration of muscle fibers.


1982 ◽  
Vol 242 (5) ◽  
pp. C272-C277 ◽  
Author(s):  
J. Henriksson ◽  
H. Galbo ◽  
E. Blomstrand

The sciatic nerve was cut on one side in 11 male cats, and a piece of the nerve was removed. The cats were then divided at random into two groups, a stimulation group (S) of five cats and a control group (C) of six cats. Bilateral electrical stimulation (2 Hz) of the gastrocnemius muscle (directly or via the motor nerve) was carried out in the S cats 4 h/day, 3 days/wk for 4 wk. The voltage delivered was adjusted in each cat so that both gastrocnemius muscles lifted identical loads the same distance. The activity of the tricarboxylic acid cycle marker enzyme succinate dehydrogenase (SDH) per unit of muscle weight more than doubled in response to stimulation both in the intact and the denervated gastrocnemius muscle. Stimulation did not affect the activity of the glycolytic marker enzyme 6-phosphofructokinase (PFK) or muscle capillarization. Denervation resulted in pronounced (approx 50%) fiber atrophy, which was not prevented by the stimulation. It is concluded that the presence of the motor nerve per se is not necessary for an activity-induced adaptation of the oxidative capacity of skeletal muscle.


2016 ◽  
Vol 8 (2) ◽  
pp. 216-225 ◽  
Author(s):  
R. Vidal-Santos ◽  
F. N. Macedo ◽  
M. N. S. Santana ◽  
V. U. De Melo ◽  
J. L. de Brito Alves ◽  
...  

The present study investigated the impact of a western diet during gestation and lactation on the anthropometry, serum biochemical, blood pressure and cardiovascular autonomic control on the offspring. Male Wistar rats were divided into two groups according to their mother’s diet received: control group (C: 18% calories of lipids) and westernized group (W: 32% calories of lipids). After weaning both groups received standard diet. On the 60th day of life, blood samples were collected for the analysis of fasting glucose and lipidogram. Cardiovascular parameters were measured on the same period. Autonomic nervous system modulation was evaluated by spectrum analysis of heart rate (HR) and systolic arterial pressure (SAP). The W increased glycemia (123±2v. 155±2 mg/dl), low-density lipoprotein (15±1v. 31±2 mg/dl), triglycerides (49±1v. 85±2 mg/dl), total cholesterol (75±2v. 86±2 mg/dl), and decreased high-density lipoprotein (50±4v. 38±3 mg/dl), as well as increased body mass (209±4v. 229±6 g) than C. Furthermore, the W showed higher SAP (130±4v. 157±2 mmHg), HR (357±10v. 428±14 bpm), sympathetic modulation to vessels (2.3±0.56v. 6±0.84 mmHg2) and LF/HF ratio (0.15±0.01v. 0.7±0.2) than C. These findings suggest that a western diet during pregnancy and lactation leads to overweight associated with autonomic misbalance and hypertension in adulthood.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Damian Jozef Flis ◽  
Robert Antoni Olek ◽  
Jan Jacek Kaczor ◽  
Ewa Rodziewicz ◽  
Malgorzata Halon ◽  
...  

The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.


2019 ◽  
Vol 242 (2) ◽  
pp. 25-36
Author(s):  
Isis Gabrielli Barbieri de Oliveira ◽  
Marcos Divino Ferreira Junior ◽  
Paulo Ricardo Lopes ◽  
Dhiogenes Balsanufo Taveira Campos ◽  
Marcos Luiz Ferreira-Neto ◽  
...  

Disruptions in circadian rhythms have been associated with several diseases, including cardiovascular and metabolic disorders. Forced internal desynchronization induced by a period of T-cycles of 22 h (T22 protocol) reaches the lower limit of entrainment and dissociates the circadian rhythmicity of the locomotor activity into two components, driven by different outputs from the suprachiasmatic nucleus (SCN). The main goal of this study was to evaluate the cardiovascular and metabolic response in rats submitted to internal desynchronization by T22 protocol. Male Wistar rats were assigned to either a control group subjected to a usual T-cycles of 24 h (12 h–12 h) or an experimental group subjected to the T22 protocol involving a 22-h symmetric light–dark cycle (11 h–11 h). After 8 weeks, rats subjected to the T22 exhibited desynchrony in their locomotor activity. Although plasma glucose and insulin levels were similar in both groups, desynchronized rats demonstrated dyslipidemia, significant hypertrophy of the fasciculate zone of the adrenal gland, low IRB, IRS2, PI3K, AKT, SOD and CAT protein expression and an increased expression of phosphoenolpyruvate carboxykinase in the liver. Furthermore, though they maintained normal baseline heart rates and mean arterial pressure levels, they also presented reduced baroreflex sensitivity. The findings indicate that circadian timing desynchrony following the T22 protocol can induce cardiometabolic disruptions. Early hepatic metabolism dysfunction can trigger other disorders, though additional studies are needed to clarify the causes.


2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Bill C. A. Bogar ◽  
Lydia Tendean ◽  
Grace L. A. Turalaki

Abstract: Infertility is an inability of couples to reproduce after carrying out sexual intercourses for at least a year without using any contraceptives. There are 10-15% couples worldwide who experience infertility problems and almost one half of them is on men. Spermatozoa qualities including concentration, motility, and morphology are used as an indicator for men’s fertility. The utilization of herbal medicine (i.e. Eurycoma longifolia Jack extracts) is now being an alternative way to improve fertility among the community. This study was carried out to find the effects of Eurycoma longifolia Jack on spermatozoa qualities. This experimental study was conducted to nine male wistar rats (Rattus norvegicus) weighing from 200-250 grams, aging from 12-15 months. These nine adult rats were divided into 3 groups of 3 rats each. 400 and 600 mg/kg/day of Eurycoma longifolia Jack extracts were orally administrated to group 1 and 2 respectively, while group 3 were treated as control group. After 50 days, the animals of group 1, 2 and 3 were sacrificed. As a result, there is an improvement in qualities of spermatozoa which are statistically significant (p<0,05) in group 2. Thus, provide the beneficial effects of 600mg/kg Eurycoma longifolia Jack extracts on the qualities of spermatozoa.Keywords: pasak bumi, spermatozoaAbstrak: Infertilitas adalah ketidakmampuan pasangan untuk dapat hamil setelah satu tahun berhubungan intim tanpa menggunakan kontrasepsi. Ada sekitar 10 – 15 % pasangan mengalami masalah infertilitas dan hampir setengahnya masalah ada pada pria. Kualitas spermatozoa meliputi konsentrasi, motilitas dan morfologi spermatozoa merupakan salah satu indikator fertilitas pada pria. Penggunaan tanaman herbal atau yang lebih dikenal jamu telah menjadi pengobatan alternatif di masyarakat. Tanaman herbal yang dimaksud adalah pasak bumi. Penelitian ini bertujuan untuk mengetahui efek dari esktrak pasak bumi (Eurycoma longifolia Jack) terhadap kualitas spermatozoa. Penelitian ini menggunakan 9 ekor tikus wistar jantan (Rattus norvegicus) dengan berat badan 200-250 g berumur 12-15 bulan. Sembilan ekor wistar dibagi menjadi tiga kelompok, dan satu kelompok terdiri dari tiga ekor tikus wistar. Penelitian ini dilaksankan selama 50 hari. Esktrak pasak bumi (Eurycoma longifolia Jack) diberikan dengan dosis 400mg/kgBB per hari pada perlakuan 1 dan dosis 600 mg/kgBB per hari pada perlakuan 2. Setelah 50 hari hewan coba pada kelompok kontrol, perlakuan 1 dan perlakuan 2 diterminasi. Hasil penelitian memperlihatkan terjadi peningkatan kualitas spermatozoa yang signifikan secara statistik (p<0,05) pada perlakuan 2 terhadap kelompok kontrol. Hasil tersebut menunjukan bahwa Esktrak pasak bumi (Eurycoma longifolia Jack) pada dosis 600 mg/kgBB dapat meningkatkan kualitas spermatozoa.Kata kunci: pasak bumi, spermatozoa


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