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Cyclosporine-induced renal artery smooth muscle contraction is associated with increases in the phosphorylation of specific contractile regulatory proteins.

Cyclosporine A (CSA) is a type 2B phosphatase inhibitor which can induce contraction of renal artery smooth muscle. In this investigation, we examined the phosphorylation events associated with CSA-induced contraction of bovine renal artery smooth muscle. Contractile responses were determined in a muscle bath and the corresponding phosphorylation events were determined with whole cell phosphorylation and two-dimensional gel electrophoresis. CSA-induced contractions were associated with increases in the phosphorylation of the 20 kDa myosin light chains (MLC20) and different isoforms of the small heat shock protein, HSP27. Cyclic nucleotide-dependent relaxation of CSA-induced contractions was associated with increases in the phosphorylation of another small heat shock protein, HSP20, and decreases in the phosphorylation of the MLC20, and some isoforms of HSP27. These data suggest that CSA-induced contraction and relaxation of vascular smooth muscle is associated with increases in the phosphorylation of specific contractile regulatory proteins.

Animals↗

Amino acid transport during muscle contraction and its relevance to exercise.

The functional significance of amino acid transport in skeletal muscle has been explored by the use of a variety of techniques including work in isolated perfused organs, isolated incubated organs and tissue culture of muscle cells. The results suggest that although there is a wide variety of amino acid transport systems of different characteristics and with different responses to ionic, hormonal and nervous modulation, the amino acid glutamine (transported by system Nm) demonstrates some unusual properties not observed with amino acids transported by other systems. Glutamine is transported at very high rates in skeletal muscle and heart and both the glutamate and glutamine transporter appear to be adaptively regulated by the availability of glutamine. Glutamine appears to be involved in the regulation of a number of important metabolic processes in heart and skeletal muscle (e.g., regulation of the glutathione reduced/oxidised ratio and regulation of protein and glycogen synthesis). Furthermore, glutamine transport appears to interact with systems for regulation of volume control and many of the metabolic features attributable to changes in glutamine concentration appear to be modulated via alteration in cytoskeletal status.

Amino Acids↗

Amphidinolide B, a powerful activator of actomyosin ATPase enhances skeletal muscle contraction.

Amphidinolide B caused a concentration-dependent increase in the contractile force of skeletal muscle skinned fibers. The concentration-contractile response curve for external Ca2+ was shifted to the left in a parallel manner, suggesting an increase in Ca2+ sensitivity. Amphidinolide B stimulated the superprecipitation of natural actomyosin. The maximum response of natural actomyosin to Ca2+ in superprecipitation was enhanced by it. Amphidinolide B increased the ATPase activity of myofibrils and natural actomyosin. The ATPase activity of actomyosin reconstituted from actin and myosin was enhanced in a concentration-dependent manner in the presence or absence of troponin-tropomyosin complex. Ca2+-, K+-EDTA- or Mg2+-ATPase of myosin was not affected by amphidinolide B. These results suggest that amphidinolide B enhances an interaction of actin and myosin directly and increases Ca2+ sensitivity of the contractile apparatus mediated through troponin-tropomyosin system, resulting in an increase in the ATPase activity of actomyosin and thus enhances the contractile response of myofilament.

Actomyosin↗

Enhanced permeability to sugar associated with muscle contraction. Studies of the role of Ca++.

When contractures were induced in isolated frog sartorius muscles with 4 mM caffeine, there was an increase in permeability of the muscle cells to 3-methylglucose. This observation suggests that the changes in permeability to sugar that are known to occur in electrically stimulated muscles may not be intimately related to the depolarization phase of the tissue response. Contractures that were elicited by exposing the muscles to a high concentration of K+ were also associated with an increased permeability to sugar. As the concentration of 45Ca in the medium was raised, more 45Ca entered the muscles during potassium contractures, and the contractures lasted longer, in agreement with the observations of other investigators. There was also a greater change in permeability to sugar when potassium contractures were elicited in the presence of higher concentrations of Ca++. The possibility that the enhanced permeability to sugar may be related to changes in the intracellular concentration of Ca++ is discussed.

3-O-Methylglucose↗

Molecular forces involved in force generation during skeletal muscle contraction.

Recent advances in protein chemistry and the kinetic analysis of tension transients in skeletal muscle fibres have enabled us to elucidate the molecular forces involved in force generation by cross-bridges. On the basis of the temperature effect, we conclude that the elementary step that generates force is an endothermic reaction (the enthalpy change delta H degree = 124 kJ mol-1 at 15 degrees C), which accompanies a large entropy increase (delta S degree = 430JK-1 mol-1) and a reduction in the heat capacity (delta C p = -6.4kJ K-1 mol-1). Thus, it can be concluded that the force-generating step is an entropy-driven reaction. The above results suggest that hydrophobic interactions are the primary cause of force generation, and that polar interactions (hydrogen bonding and charge interactions) are involved to a lesser degree. On the basis of the thermodynamic data, we estimate that during force generation approximately 50 nm2 of surface area is involved for hydrophobic interactions and another 30 nm2 for polar interactions. These data suggest that both the actomyosin interaction and the cleft closure of the myosin head are essential for force generation.

Actins↗

[Functional roles of cyclic AMP and cyclic GMP on rabbit urinary bladder and urethral smooth muscle contraction].

It is suggested that cyclic AMP and cyclic GMP play regulatory roles in smooth muscle function. In order to clarify the role of cyclic AMP and cyclic GMP in the function of the lower urinary tract, I examined the effects of isoproterenol and sodium nitroprusside on contractile force and tissue content of cyclic AMP and cyclic GMP. Isoproterenol (10(-8)-10(-4) M) caused a relaxing effect in the rabbit urinary bladder dome, the bladder base and the urethra. The relaxation response by isoproterenol was mediated by cyclic AMP. The relaxation response and the increase in the cyclic AMP level were marked in the bladder dome. Sodium nitroprusside (10(-8)-10(-4) M) also caused a relaxing effect in the rabbit urinary bladder dome, the bladder base and the urethra. The relaxation response to sodium nitroprusside was mediated by cyclic GMP. The relaxation response and the increase in the cyclic GMP level were marked in the urethra. The external addition of derivatives of cyclic AMP and cyclic GMP (dibutyryl cyclic AMP and 8-bromo cyclic GMP, 10(-8)-10(-3) M) also caused a relaxing effect in the bladder dome, the bladder base and the urethra. These results demonstrated that both cyclic AMP and cyclic GMP were related to relaxation of the rabbit lower urinary tract smooth muscle. It seems that cyclic AMP may be mainly related to relaxation of the bladder dome and cyclic GMP may be mainly related to relaxation of the urethra.

Animals↗

Reduced arteriolar responses to skeletal muscle contraction after ingestion of a high salt diet.

We previously reported that in skeletal muscle arterioles of rats fed a very high salt (HS; 7%) diet, the bioavailability of endothelium-derived nitric oxide (NO) is reduced through scavenging by reactive oxygen species. Because arteriolar NO can play an important role in local blood flow control, we investigated whether arteriolar responses to increased tissue metabolism become compromised in skeletal muscle of salt-fed rats. Consumption of a HS (4%) diet for 4 weeks had no effect on arteriolar diameters, volume flow or shear stress in resting spinotrapezius muscle. Arteriolar responses to a modest elevation in metabolic demand (0.5 Hz contraction) were not different from those in rats fed a normal diet, but diameter responses to a greater elevation in metabolic demand (4 Hz contraction) were significantly less in HS rats than in rats fed a normal diet. In both groups, the NO synthase inhibitor N(G)-monomethyl-L-arginine reduced resting arteriolar diameters and flow by a similar amount and had little or no effect on arteriolar diameter or flow responses to muscle contraction. Arterioles in HS rats exhibited an increase in overall oxidant activity (tetranitroblue tetrazolium reduction) but not in superoxide activity (dihydroethidine oxidation). Reactive oxygen species scavengers (2,2,6,6-tetramethylpiperidine-N-oxyl and catalase) did not normalize the reduced arteriolar responses to muscle contraction in HS rats. These findings suggest that increased oxidant activity in the arteriolar network of salt-fed rats is not due to accumulation of superoxide anion and that neither this oxidant activity nor reduced NO availability can account for the blunted active arteriolar dilation in rats fed a 4% salt diet.

Animals↗

Diagnosis and treatment of muscle contraction (tension-type) headaches.

Acute tension-type headache is a very common condition that rarely is a problem in treatment. Chronic tension-type headache, however, is often a difficult therapeutic problem. The pathogenesis is not well understood, but both peripheral muscle contraction and central pain-modulating systems are probably involved. Therapy usually works best when multiple techniques are used, including pharmacologic, psychological, and physiologic modalities.

Headache↗

Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections.

Immune responses associated with intestinal nematode infections are characterized by the activation of T-helper 2 (Th2) cells. Previous studies demonstrated that during Trichinella spiralis infection, Th2 cells contribute to the development of intestinal muscle hypercontractility and to worm eviction from the gut, in part through signal transducer and activator of transcription factor 6 (Stat6). Interleukin-9 (IL-9), a Th2-cell-derived cytokine, has pleiotropic activities on various cells that are not mediated through Stat6. In this study, we investigated the role of IL-9 in the generation of enteric muscle hypercontractility in mice infected with the intestinal parasite T. spiralis and the cecal parasite Trichuris muris. Treatment of mice with IL-9 enhanced infection-induced jejunal muscle hypercontractility and accelerated worm expulsion in T. spiralis infection. These effects were associated with an up-regulation of IL-4 and IL-13 production from in vitro-stimulated spleen cells. In addition, increases in the level of intestinal goblet cells and in the level of mouse mucosal mast cell protease 1 (MMCP-1) in serum were observed in infected mice following IL-9 administration. However, the neutralization of IL-9 by anti-IL-9 vaccination or by anti-IL-9 antibody had no significant effect on worm expulsion or muscle contraction in T. spiralis-infected mice. In contrast, the neutralization of IL-9 significantly attenuated T. muris infection-induced colonic muscle hypercontractility and inhibited worm expulsion. The attenuated expulsion of the parasite by IL-9 neutralization was not accompanied by changes in goblet cell hyperplasia or the MMCP-1 level. These findings suggest that IL-9 contributes to intestinal muscle function and to host protective immunity and that its importance and contribution may differ depending on the type of nematode infection.

Animals↗

[Accuracy of determining sarcomere lengths in contracted muscle by laser diffraction method].

The method of laser diffraction by cross-striated muscle was used to investigate changes of sarcomere lengths during contraction. The development of muscle tension was recorded simultaneously with length measurings. The changes of the sarcomere length were determined from angular displacement between the left (+1)- and right-(-1)-first order maximums. The absolute error is less than 0.65 micrometer for the sarcomere lengths 1.8--2.8 micrometers and for the lengths 2.8--3.3 micrometers it is less than 0.1 micrometer. The resolution of length changes is under 0.003 micrometer over the whole range. It was shown that not only the positions of (+1)- and (-1))-diffraction maximums were displaced, but the position of zero order diffraction maximum might be changed. We explained this phenomenon in terms of form changes of the illuminated region of the fiber.

Animals↗

Quantitative research for improving respiratory muscle contraction by breathing exercise.

OBJECTIVE: To investigate the effects of breathing exercise on chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: 324 patients stable COPD were randomly assigned to either the breathing exercise group (Group I) or control group consisting of placebo (Group II). The maximum respiratory pressure (320 cases) and transdiaphragmatic pressure (129 cases) were monitored via RMS-I and Type-2 pressure measurements. The breathing exercises were taught and checked by experienced specialists periodically. Comparison was made between Group I and Group II using maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), diaphragmatic pressure (Pdi) and maximum transdiaphragmatic pressure (Pdimax) after 1 to 20 months. RESULTS: In Group I MIP increased by 30.42%, MEP 32.10%, Pdi 30.94% and Pdimax 65.59% (P < 0.001). No significant changes were observed in Group II given the placebo. The MIP, MEP, Pdi and Pdimax were 6.95%, 2.92%, 14.63 and 9.05% respectively (P > 0.05). CONCLUSIONS: Breathing exercise has a potent and long lasting effect on respiratory muscle contraction. The methods mentioned above can be used as standard quantitative index for contractile properties of respiratory muscle.

Aged↗