Nonuniform changes in arteriolar myogenic tone within skeletal muscle following hindlimb unweighting

2002 ◽  
Vol 92 (3) ◽  
pp. 1145-1151 ◽  
Author(s):  
Cristine L. Heaps ◽  
Douglas K. Bowles

Hindlimb unweighting (HLU) has been shown to alter myogenic tone distinctly in arterioles isolated from skeletal muscles composed predominantly of fast-twitch (white gastrocnemius) compared with slow-twitch (soleus) fibers. Based on these findings, we hypothesized that HLU would alter myogenic tone differently in arterioles isolated from distinct fiber-type regions within a single skeletal muscle. We further hypothesized that alterations in myogenic tone would be associated with alterations in voltage-gated Ca2+ channel current (VGCC) density of arteriolar smooth muscle. After 14 days of HLU or weight bearing (control), first-order arterioles were isolated from both fast-twitch and mixed fiber-type regions of the gastrocnemius muscle, cannulated, and pressurized at 90 cmH2O. Mixed gastrocnemius arterioles of HLU rats demonstrated increased spontaneous tone [43 ± 5% (HLU) vs. 27 ± 4% (control) of possible constriction] and an approximately twofold enhanced myogenic response when exposed to step changes in intraluminal pressure (10–130 cmH2O) compared with control rats. In contrast, fast-twitch gastrocnemius arterioles of HLU rats demonstrated similar levels of spontaneous tone [6 ± 2% (HLU) vs. 6 ± 2% (control)] and myogenic reactivity to control rats. Neither KCl-induced contractile responses (10–50 mM KCl) nor VGCC density was significantly different between mixed gastrocnemius arterioles of HLU and control rats. These results suggest that HLU produces diverse adaptations in myogenic reactivity of arterioles isolated from different fiber-type regions of a single skeletal muscle. Furthermore, alterations in myogenic responses were not attributable to altered VGCC density.

1988 ◽  
Vol 254 (5) ◽  
pp. C651-C656 ◽  
Author(s):  
P. Babij ◽  
F. W. Booth

Specific complementary DNA (cDNA) hybridization probes were used to estimate the levels of alpha-actin and cytochrome c mRNAs and also 18S rRNA in three models of skeletal muscle atrophy. After 7 days of hindlimb suspension, or immobilization, or denervation, protein content decreased 26-32% in all muscles studied except suspended fast-twitch muscle, which lost only half as much protein. alpha-Actin mRNA content decreased 51-66% and cytochrome c mRNA content decreased 42-61% in slow- and fast-twitch muscles in all three models of atrophy. However, total RNA content did not show similar directional changes; RNA content decreased 27-44% in suspended and immobilized muscle but was unchanged in denervated fast-twitch muscle. The results were interpreted to suggest that loss of weight-bearing function of skeletal muscle is a major factor affecting the levels of alpha-actin and cytochrome c mRNAs during muscle atrophy.


1983 ◽  
Vol 245 (2) ◽  
pp. H265-H275 ◽  
Author(s):  
B. G. Mackie ◽  
R. L. Terjung

Blood flow to fast-twitch red (FTR), fast-twitch white (FTW), and slow-twitch red (STR) muscle fiber sections of the gastrocnemius-plantaris-soleus muscle group was determined using 15 +/- 3-microns microspheres during in situ stimulation in pentobarbital-anesthetized rats. Steady-state blood flows were assessed during the 10th min of contraction using twitch (0.1, 0.5, 1, 3, and 5 Hz) and tetanic (7.5, 15, 30, 60, and 120/min) stimulation conditions. In addition, an earlier blood flow determination was begun at 3 min (twitch series) or at 30 s (tetanic series) of stimulation. Blood flow was highest in the FTR (220-240 ml X min-1 X 100 g-1), intermediate in the STR (140), and lowest in the FTW (70-80) section during tetanic contraction conditions estimated to coincide with the peak aerobic function of each fiber type. These blood flows are fairly proportional to the differences in oxidative capacity among fiber types. Further, their absolute values are similar to those predicted from the relationship between blood flow and oxidative capacity found by others for dog and cat muscles. During low-frequency contraction conditions, initial blood flow to the FTR and STR sections were excessively high and not dependent on contraction frequency. However, blood flows subsequently decreased to values in keeping with the relative energy demands. In contrast, FTW muscle did not exhibit this time-dependent relative hyperemia. Thus, besides the obvious quantitative differences between skeletal muscle fiber types, there are qualitative differences in blood flow response during contractions. Our findings establish that, based on fiber type composition, a heterogeneity in blood flow distribution can occur within a whole muscle during contraction.


2009 ◽  
Vol 107 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Lori S. Kang ◽  
SeJeong Kim ◽  
James M. Dominguez ◽  
Amy L. Sindler ◽  
Gregory M. Dick ◽  
...  

Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent evidence indicates that both large-conductance Ca2+-activated (BKCa) and voltage-dependent (KV) K+ channels mediate negative feedback control of the myogenic response. Thus we tested the hypothesis that aging increases the contributions of KV and BKCa channels to myogenic regulation of vascular tone. Because myogenic responsiveness differs between oxidative and glycolytic muscles, we predicted that KV and BKCa channel contributions to myogenic responsiveness vary with fiber type. Myogenic responses of first-order arterioles from the gastrocnemius and soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors of KV and BKCa, respectively. 4-Aminopyridine enhanced myogenic tone with aging and normalized age-related differences in both muscle types. By contrast, iberiotoxin eliminated age-related differences in soleus arterioles and had no effect in gastrocnemius vessels. KV1.5 is an integral component of KV channels in vascular smooth muscle; therefore, we determined the relative protein expression of KV1.5, as well as BKCa, in soleus and gastrocnemius arterioles. Immunoblot analysis revealed no differences in KV1.5 protein with aging or between variant fiber types, whereas BKCa protein levels declined with age in arterioles from both muscle groups. Collectively, these results suggest that the contribution of BKCa to myogenic regulation of vascular tone changes with age in soleus muscle arterioles, whereas increased KV channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.


2000 ◽  
Vol 279 (5) ◽  
pp. R1889-R1898 ◽  
Author(s):  
Jeffery Morrissette ◽  
Le Xu ◽  
Alexandra Nelson ◽  
Gerhard Meissner ◽  
Barbara A. Block

Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type–specific manner in fish skeletal muscle (11). In this study, we compare [3H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [3H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (Po) of RyR1-slow was threefold less than the maximum Po of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest Po of all the RyR channels and displayed less inhibition at millimolar Ca2+. The addition of 5 mM Mg-ATP or 2.5 mM β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP) to the channels increased the Po and [3H]ryanodine binding of both RyR1s but also caused a shift in the Ca2+ dependency curve of RyR1-slow such that Ca2+-dependent inactivation was attenuated. [3H]ryanodine binding data also showed that Mg2+-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca2+ is regulated in these muscle types.


2001 ◽  
Vol 155 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Yewei Liu ◽  
Zoltán Cseresnyés ◽  
William R. Randall ◽  
Martin F. Schneider

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.


1998 ◽  
Vol 275 (3) ◽  
pp. E487-E494 ◽  
Author(s):  
Anne Raben ◽  
Elsebeth Mygind ◽  
Arne Astrup

Muscle fiber morphology and activities of four key enzymes, as well as energy metabolism, were determined in nine normal-weight postobese women and nine matched control subjects. No differences in fiber type composition, but a smaller mean fiber area and area of fiber types I and IIb, were found in postobese compared with control subjects ( P < 0.05). The activities of β-hydroxyacyl-CoA dehydrogenase (HADH) and citrate synthase (CS) were 20% lower in postobese than in control subjects ( P < 0.05). However, the activities of lactate dehydrogenase and lipoprotein lipase were not significantly different between postobese and control subjects. Basal metabolic rate and respiratory exchange ratio were also similar, but maximal oxygen uptake (V˙o 2 max) tended to be lower in postobese than in control subjects ( P = 0.06). When adjustments were made for differences inV˙o 2 max, HADH and CS were not different between postobese and control subjects. In conclusion, these data suggest that smaller fiber areas and lower enzyme activities, i.e., markers of aerobic capacity of skeletal muscle, but not fiber composition, may be factors predisposing to obesity.


1991 ◽  
Vol 260 (1) ◽  
pp. H130-H135 ◽  
Author(s):  
J. C. Falcone ◽  
M. J. Davis ◽  
G. A. Meininger

The goal of this study was to determine whether the endothelium played a role in the myogenic response of skeletal muscle arterioles. First-order arterioles (n = 15) were isolated from the rat cremaster muscle and cannulated for in vitro study. The development of spontaneous tone reduced the diameter of the isolated arterioles from 166.7 +/- 7.6 microns to 89.2 +/- 7.2 microns. The arterioles were exposed to step changes in intraluminal pressure over a range of 10–170 cmH2O and had no flow through their lumen. The vessels exhibited active constriction to step increases or active dilation to step decreases in pressure (50–150 cmH2O). At 90 cmH2O, arterioles dilated by 89.2 +/- 6.0% in response to the endothelium-dependent vasodilator acetylcholine (10(-6) M; ACh) and 89.6 +/- 10.9% in response to endothelium-independent dilator adenosine (10(-4) M; Ado). The endothelium was physically denuded by rubbing the vessel lumen. After denudation, the arteriolar dilation to ACh was abolished, whereas the dilation to Ado was unaltered. The absence of endothelium was verified by electron microscopy. Basal tone and the response to changes in pressure were not significantly different from endothelium-intact vessels. These studies indicate that the endothelium is not responsible for myogenic activity or development of spontaneous tone in skeletal muscle arterioles.


2005 ◽  
Vol 289 (1) ◽  
pp. H322-H329 ◽  
Author(s):  
Luis A. Martinez-Lemus ◽  
Tracy Crow ◽  
Michael J. Davis ◽  
Gerald A. Meininger

In isolated resistance arterioles with spontaneous tone, ligation of α4β1- and α5β1-integrins induces vasoconstriction whereas ligation of αvβ3-integrin induces vasodilation. However, whether integrins directly participate in myogenic constriction to pressure elevation is not known. To answer this question, isolated rat skeletal muscle arterioles were exposed to step increments in pressure in the absence or presence of peptides and function-blocking antibodies known to bind α4β1-, α5β1-, or αvβ3-integrins while vessel diameter was continually monitored. Myogenic constriction, as assessed by the ability of isolated arterioles to reduce their diameter in response to two consecutive increments in intraluminal pressure (90–110 and 110–130 cmH2O), was not affected by treatment with any of the control peptides (RAD, LEV), a control antibody (anti-rat major histocompatibility complex), an α4β1-integrin-binding peptide (LDV), or an anti-α4-integrin antibody. In contrast, α5β1-integrin blockade with either anti-α5- or anti-β1-integrin antibody caused a significant inhibition of myogenic constriction. Also, both RGD peptide and anti-β3-integrin antibody inhibited myogenic constriction. These results indicate that α5β1- and αvβ3-integrins are necessary for myogenic constriction and further suggest that integrins are part of the mechanosensory apparatus responsible for the ability of vascular smooth muscle cells to detect and/or respond to changes in intraluminal pressure.


2007 ◽  
Vol 28 (3) ◽  
pp. 253-272 ◽  
Author(s):  
Tony Vuocolo ◽  
Keren Byrne ◽  
Jason White ◽  
Sean McWilliam ◽  
Antonio Reverter ◽  
...  

The callipyge mutation in sheep results in postnatal skeletal muscle hypertrophy in the pelvic limbs and loins with little or no effect on anterior skeletal muscles. Associated with the phenotype are changes in the expression of a number of imprinted genes flanking the site of the mutation, which lies in an intergenic region at the telomeric end of ovine chromosome 18. The manner in which these local changes in gene expression are translated into muscle hypertrophy is not known. Microarray-based transcriptional profiling was used to identify differentially expressed genes in longissimus dorsi skeletal muscle samples taken at birth and 12 wk of age from callipyge and wild-type sheep. The phenotype was only expressed at the latter developmental time and associated with decreased type 1 fibers (slow oxidative) and a shift toward type IIx and IIb fibers (fast-twitch glycolytic). We have identified 131 genes in the samples taken at 12 wk of age that were differentially expressed as a function of genotype but not due to the fiber type changes. The gene expression changes occurring as a function of genotype in the samples taken at birth indicated that the transcriptional framework underpinning the phenotype was emerging prior to expression of the phenotype. Eight genes were differentially expressed as a function of genotype at both developmental times. A model is proposed describing a core network of genes and histone epigenetic modifications that is likely to underpin the fiber type changes and muscle hypertrophy characteristic of callipyge sheep.


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