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At least 1,171 records · Page 65Linked to original sources
PubMed2003

The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction.

A variety of contractile agonists trigger activation of the small GTPase RhoA. An important target of activated RhoA in smooth muscle is Rho-associated kinase (ROK), one of the downstream targets that is the myosin binding subunit (MYPT1) of myosin light chain phosphatase (MLCP). Phosphorylation of MYPT1 at T695 by activated ROK results in a decrease in phosphatase activity of MLCP and an increase in myosin light chain (LC(20)) phosphorylation catalyzed by Ca(2)(+)/calmodulin-dependent myosin light chain kinase and/or a distinct Ca(2)(+)-independent kinase. LC(20) phosphorylation in turn triggers cross-bridge cycling and force development. ROK also phosphorylates the cytosolic protein CPI-17 (at T38), which thereby becomes a potent inhibitor of MLCP. The RhoA/ROK pathway has been implicated in the tonic phase of force maintenance in response to various agonists, with no evident role in the phasic response, suggesting this pathway as a potential target for antihypertensive therapy. Indeed, ROK inhibitors restore normal blood pressure in several rat hypertensive models.

Animals↗
PubMed1999

Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats.

Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway smooth muscle contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.

Acetylcholine↗
PubMed1993

Effects of muscle contraction on cytochrome a,a3 redox state.

The relationships among mitochondrial O2 availability, O2 delivery, and lactate formation in exercising skeletal muscle remain unclear. Some data suggest that muscle O2 provision is sufficient at maximal O2 consumption (VO2max) to challenge the concept of a mitochondrial O2 limitation at VO2max. The relationships among VO2, mitochondrial O2 availability, and net lactate production were studied over a wide range of exercise intensities. Using near-infrared spectroscopy, the oxidation-reduction state of cytochrome a,a3 was monitored in the canine gracilis in vivo. Twenty adult dogs were anesthetized with alpha-chloralose, intubated, and mechanically ventilated on room air. Five-minute stimulation periods at rates of 2, 3, 4, 5, 7, 8, 10, or 12 stimuli/s were performed. VO2max generally was achieved at a stimulation rate of 8 stimuli/s; mean VO2max was 0.12 +/- 0.09 (SE) ml.min-1 x g-1. The concentration of oxidized mitochondrial cytochrome a,a3 decreased at all work loads relative to resting state and demonstrated a near-linear relationship with muscle VO2 (r2 = 0.99). Muscle lactate efflux and the lactate-pyruvate ratio also were correlated positively with cytochrome a,a3 reduction, suggesting a common regulatory mechanism coupling the processes of aerobic glycolysis and oxidative phosphorylation. At VO2max, the corresponding cytochrome oxidation was not significantly different from that observed at death. Thus, in the gracilis maximal exercise leads to near-complete reduction of cytochrome a,a3 secondary to deficient O2 provision. We conclude that VO2max is limited primarily by O2 delivery to this muscle and not by other factors limiting mitochondrial ATP production or substrate oxidation.

Animals↗
PubMed1999

Training-induced elevation in FABP(PM) is associated with increased palmitate use in contracting muscle.

To evaluate the effects of endurance training in rats on fatty acid metabolism, we measured the uptake and oxidation of palmitate in isolated rat hindquarters as well as the content of fatty acid-binding proteins in the plasma membranes (FABP(PM)) of red and white muscles from 16 trained (T) and 18 untrained (UT) rats. Hindquarters were perfused with 6 mM glucose, 1,800 microM palmitate, and [1-(14)C]palmitate at rest and during electrical stimulation (ES) for 25 min. FABP(PM) content was 43-226% higher in red than in white muscles and was increased by 55% in red muscles after training. A positive correlation was found to exist between succinate dehydrogenase activity and FABP(PM) content in muscle. Palmitate uptake increased by 64-73% from rest to ES in both T and UT and was 48-57% higher in T than UT both at rest (39.8 +/- 3.5 vs. 26.9 +/- 4. 4 nmol. min(-1). g(-1), T and UT, respectively) and during ES (69.0 +/- 6.1 vs. 43.9 +/- 4.4 nmol. min(-1). g(-1), T and UT, respectively). While the rats were resting, palmitate oxidation was not affected by training; palmitate oxidation during ES was higher in T than UT rats (14.8 +/- 1.3 vs. 9.3 +/- 1.9 nmol. min(-1). g(-1), T and UT, respectively). In conclusion, endurance training increases 1) plasma free fatty acid (FFA) uptake in resting and contracting perfused muscle, 2) plasma FFA oxidation in contracting perfused muscle, and 3) FABP(PM) content in red muscles. These results suggest that an increased number of these putative plasma membrane fatty acid transporters may be available in the trained muscle and may be implicated in the regulation of plasma FFA metabolism in skeletal muscle.

5'-Nucleotidase↗
PubMed2005

Fibre-type specificity of interleukin-6 gene transcription during muscle contraction in rat: association with calcineurin activity.

In this study, we quantified the transcription of the interleukin-6 (IL-6) gene in individual fibres and the associated changes in calcineurin activity assessed at the cellular level during prolonged muscle contraction. Individual myofibres were isolated from plantaris and soleus muscles of rats at the end of an exhaustive running exercise test (n = 10), categorized according to their myosin heavy chain isoform content, and compared to those of resting rats (n = 10). Using real-time PCR analysis in individual fibres, a marked rise in IL-6 transcript levels occurred in type I and IIa fibres at the end of exercise (P < 0.05). Transcription of the gene encoding for the modulatory calcineurin-interacting protein-1 (MCIP-1), a sensitive indicator of calcineurin activity, also mainly increased in type I and IIa fibres (P < 0.05). Moreover, a slight increase in MCIP-1 mRNA levels was observed in type IIx (P < 0.05). Fibre types determined by immunohistochemistry were qualitatively examined for glycogen content using periodic acid-Shiff staining, and no direct relationship was found, at the cellular level, between glycogen content, fibre-type and IL-6 transcription. Our data clearly suggest that IL-6 gene transcription was mainly observed in early recruited myofibres and that contraction-induced IL-6 transcription could be associated with enhanced calcineurin activity.

Adaptation, Physiological↗
PubMed1985

Electrical parameters for safe and effective electro-acupuncture and transcutaneous electrical stimulation: threshold potentials for tingling, muscle contraction and pain; and how to prevent adverse effects of electro-therapy. Part 1.

10 Essential electrical parameters for safe and effective electrical stimulation was discussed. Among them, especially importance of rise and fall time which influence capacitive current (Ic = C X dv/dt), pulse duration and output impedance for (+) and (-) polarities was emphasized. When comparing one pulse component with high amplitude with the other pulse component with low amplitude in the same stimulation pulse complex of the same electrical stimulator, effective stimulation voltage delivered to the body can be larger with the low amplitude pulse component if it has much lower output impedance than the other. When pulse repetition rate is higher than several pulses/sec., in spite of increase in pain threshold, microcirculation is often interfered with and as a result the effect will not last long after each treatment. Our studies indicate that optimal pulse repetition rate is about the same as heart rate synchronized with local circulation. Tingling threshold is a more reproducible reliable parameter than pain threshold in study of pain. Measurement of threshold potentials for tingling sensation, muscle contraction, along with pain threshold is extremely important in the same patient. Phenomena of short circuits between the nerve fibers responsible for tingling sensation and nerve fibers responsible for pain sensation is described.

Acupuncture Therapy↗
PubMed1987

Artificial reflex arc: a potential solution for chronic aspiration. I. Neck skin stimulation triggering strap muscle contraction in the canine.

Aspiration can occur when the reflex of deglutition occurring in the brain stem is impaired. Surgical procedures involving the airway have so far failed to provide a long-term solution to this problem. Because the sphincteric properties of the larynx could be used to help separate the air from the food passages on a dynamic basis, we present the concept of an artificial reflex are (ARA) in the canine. The afferent limb of this system consists in a cervical cutaneous sensory surface containing the specific biologic sensors for pressure and stretch, subtended by a corresponding sensory nerve, destined to be eventually implanted into the pharynx. The efferent limb picks up the information resulting from the sensor's distention via a frequency modulator and an amplifier, prior to transmitting it to the recurrent laryngeal nerves through monopolar electrodes, resulting in synchronous glottic closure. In order to test this new concept as a pilot study, this principle was applied in three dogs by using an island of cervical skin tubed on itself and the contralateral strap muscles as effector. Inflation of a Foley catheter introduced into the lumen of this tube resulted in synchronous strap muscle contraction, following corresponding increase in the firing frequency in the subtended sensory nerve. The data obtained in this series of experiments should permit further application at the laryngeal level.

Animals↗
PubMed1992

Blood flow during muscle contraction and relaxation in rhythmic exercise at different intensities.

Effect of contraction force on blood flow during the contraction and relaxation phase of rhythmic handgrip exercise was studied on 6 healthy women. Velocity of blood flow in the brachial artery and the diameter of the artery were studied by Doppler-ultrasound method. Both the peak and mean velocity of the blood flow were significantly higher during the relaxation period than during contraction, and the velocity during the relaxation period was significantly higher in 30% MVC exercise than in 10% MVC exercise. However, no significant differences were found in the diameter of the artery between resting and exercise conditions, nor between exercises at different intensities. Thus blood flow during the relaxation phase was significantly increased from 135.7 +/- 18.2 ml.min-1 (10% MVC) to 182.5 +/- 19.6 ml.min-1 (30% MVC) by an increased contraction force, whereas blood flow during the contraction phase was hardly affected by increased contraction force.

Adult↗
PubMed1989

Regulation mechanisms of muscle contraction at subcellular level.

The relaxation phase of contraction under voltage clamp conditions was analysed. It was shown that relaxation can be described by at least two exponentials. These can be explained as contributions of Ca uptake and Ca redistribution between the Ca specific sites on troponin C. The analysis has brought evidence in support of the hypothesis concerning unhomogenous distribution of Ca occupied sites during the activation of contraction.

Animals↗
PubMed1999

Possible involvement of K+ channel opening to the interleukin-1 beta-induced inhibition of vascular smooth muscle contraction.

We have previously shown that interleukin-1 beta relaxes vascular smooth muscle by the NO-dependent and independent mechanisms (Takizawa et al.: Eur. J. Pharmacol. 330: 143-150, 1997). In this study, we investigated the mechanism of NO-independent relaxation. Treatment of the rat aorta with interleukin-1 beta for 24 hr inhibited the high-K+ induced contraction by decreasing cytosolic Ca2+ level ([Ca2+]i). The relationship between [Ca2+]i and tension in intact muscle and the pCa-tension curves in permeabilized muscle suggested that Ca2+ sensitivity of contractile element was not changed after the interleukin-1 beta-treatment. After a treatment with interleukin-1 beta for 24 hr, contractile effects of phenylephrine (1 microM-10 microM) were markedly inhibited in the presence of L-NMMA (100 microM) applied to inhibit NO synthesis. A blocker of ATP-sensitive K+ channel, glibenclamide (1 microM), partially recovered the interleukin-1 beta-induced inhibition. In contrast, a blocker of Ca(2+)-activated K+ channel, charybdotoxin (0.1 microM), was ineffective. These results suggest that membrane hyperpolarization due to activation of ATP-sensitive K+ channels may partly be responsible for the NO-independent mechanism of interleukin-1 beta-induced inhibition of vascular smooth muscle contraction.

Animals↗
PubMed1995

Extracellular and intracellular effects of polyamines on smooth muscle contractions.

The natural polyamines spermine, spermidine and putrescine, and their metabolic products N1-acetylspermine (N-AS) and 5'-deoxi-5'-methyl-thioadenosine (DMT), but not N1-acetylspermidine nor N-acetylputrescine, relax the KCl-induced contraction in rat uterus in a dose-dependent way. This relaxing effect is counteracted by CaCl2 (0.1-6 mM) but not by Bay K 8644. Spermine, N-AS and DMT also inhibit the contraction induced by methacholine and PGF2 alpha. Spermine, DMT and N-AS relax the vanadate-induced contraction in uterus incubated in calcium-free solution plus EDTA. However, in the vanadate contraction, the EC50s are higher than those obtained with other contracturants. These results suggest that polyamines inhibit smooth muscle contraction by action at plasma membrane level decreasing the influx of calcium. However, intracellular actions of polyamines could also be involved in their effects.

Animals↗
PubMed1998

Acute and sustained effects of isometric and lengthening muscle contractions on high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC. Rat tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC. Structural muscle damage occurred only after 240 LC. The fact that tissue glycogen levels declined to a similar extent during LC and IC suggests that the energy demand was comparable during both types of exercise. Nevertheless, the observation that on the one hand tissue stores of adenine nucleotides showed a greater decline, and on the other hand the tissue content of IMP increased to a significantly higher level after LC than after IC, clearly indicates that muscle energy metabolism is more disturbed during LC than during IC. The high tissue levels of IMP may contribute to impaired mechanical function as previously observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240 LC, tissue glycogen stores and high-energy phosphate levels were not restored to control values. The present findings indicate that depressed glycogen synthase activity and impaired activity of the mitochondrial marker enzyme cytochrome C oxidase probably contribute to a continuous disturbance of energy metabolism in the exercised muscles during the 24 hours following 240 LC.

Adenosine Diphosphate↗
PubMed1994

Different effects of gradual vs. acute adenine nucleotide depletion on ATP cost of muscle contraction.

ATP and phosphocreatine (PCr) levels were chronically reduced in rat fast-twitch muscle by 40 and 87%, respectively, after rats were fed a diet containing 1% beta-guanidinopropionate (beta-GPA) for 9 wk. Myosin heavy chain distribution of superficial gastrocnemius muscle changed from 22:78% type IIA/type IIB in control to 39:61% in GPA-treated muscles. ATP cost of contractions was estimated from the PCr changes measured by gated 31P-nuclear magnetic resonance after brief (< 6 s) bursts of contractions. There was no significant change in the ATP cost of either twitch (0.3 mumol.g-1.twitch-1) or tetanic (2.5 mumol.g-1.100 ms tetanus-1) contractions in gastrocnemius muscle after chronic phosphagen depletion due to beta-GPA feeding. In two other groups of rats, ATP of gastrocnemius muscles was acutely depleted to inosine 5'-monophosphate (IMP) by tetanic stimulation. IMP reanimation was inhibited during a subsequent 75-min recovery period in one group by hadacidin treatment (100 mg/kg), resulting in 46% ATP depletion compared with the similarly stimulated and recovered control group. In contrast to gradual ATP depletion due to beta-GPA feeding, this acute ATP depletion treatment was associated with a 39% decrease in ATP cost of twitch contractions.

Adenine Nucleotides↗
PubMed1991

Modification of myosin light chain phosphorylation in sustained arterial muscle contraction by phorbol dibutyrate.

The decrease in phosphorylation of the 20 kDa myosin light chain during prolonged K(+)-stimulation of arterial smooth muscle was counteracted by treating this muscle with phorbol dibutyrate. Quantitative phosphopeptide analysis revealed that phorbol dibutyrate induced phosphorylation of serine and threonine residues in the light chain by protein kinase C and phosphorylation of a threonine residue by myosin light chain kinase. The same residues of light chain were also phosphorylated when phorbol dibutyrate was added to muscles pretreated either with the Ca2(+)-channel-blocking agents nifedipine and verapamil, or with the Ca2(+)-chelating agent ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The results indicate an interrelationship between protein kinase C and myosin light chain kinase phosphorylated sites of light chain in intact arterial smooth muscle.

Animals↗
PubMed1991

G-protein-mediated Ca2+ sensitization of smooth muscle contraction through myosin light chain phosphorylation.

The Ca2+ sensitivities of tonic (pulmonary and femoral artery) and phasic (portal vein and ileum) smooth muscles and the effects of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S) and norepinephrine on Ca2+ sensitivity of force development and myosin light chain (MLC20) phosphorylation were determined in permeabilized preparations that retained coupled receptors and endogenous calmodulin. The Ca2+ sensitivity of force was higher (approximately 3-fold) in the tonic than in the phasic smooth muscles. The nucleotide specificity of Ca2+ sensitization was: GTP gamma S much greater than GTP greater than ITP much greater than CTP = UTP. Baseline phosphorylation (7% at pCa greater than 8) and maximal phosphorylation (58% at pCa 5.0) were both lower in portal vein than in femoral artery (20 and 97%). Norepinephrine and GTP gamma S increased phosphorylation at constant [Ca2+] (pCa 7.0-6.5). MLC20 phosphorylation induced by norepinephrine was completely inhibited by guanosine 5'-O-(beta-thiodiphosphate) (GDP beta S). In portal vein at pCa 5, GTP gamma S increased phosphorylation from 58%, the maximal Ca2(+)-activated value, to 75%, and at pCa greater than 8, from 7 to 13%. In femoral artery at pCa 5, neither phosphorylation (97%) nor force was affected by GTP gamma S, while at pCa greater than 8, GTP gamma S caused an increase in force (16% of maximum) with a borderline increase in MLC20 phosphorylation (from 20 to 27%). MLC20 phosphorylation (up to 100%) was positively correlated with force. The major results support the hypothesis that the G-protein coupled Ca2(+)-sensitizing effect of agonists on force development is secondary to increased MLC20 phosphorylation.

Adrenergic alpha-Agonists↗