Effect of hindlimb unweighting on tissue blood flow in the rat.

The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported (Witzmann et al., J. Appl. Physiol. 54: 1242-1248, 1983) elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow.     

Hindlimb unweighting affects rat vascular capacitance function

Microgravity is associated with an impaired stroke volume and, therefore, cardiac output response to orthostatic stress. We hypothesized that a decreased venous filling pressure due to increased venous compliance may be an important contributing factor in this response. We used a constant flow, constant right atrial pressure cardiopulmonary bypass procedure to measure total systemic vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These compliance values were calculated under baseline conditions and during an infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in reservoir volume, which reflects changes in unstressed vascular volume (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V) were larger in HLU rats both at baseline and during the NE infusion (P < 0.05). Infusion of NE decreased C(T) and C(V) by ~20% in both HLU and control rats (P < 0.01). C(A) was also significantly decreased in both groups of rats by NE (P < 0.01), but values of C(A) were similar between HLU and control rats both at baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling pressure during orthostasis and thus may partially underlie the mechanism leading to the exaggerated fall in stroke volume and cardiac output seen in astronauts during an orthostatic stress after exposure to microgravity.     

Effect of hindlimb unweighting on anaerobic metabolism in rat skeletal muscle.

Female Sprague-Dawley rats (250 g) were hindlimb suspended for 14 days, and the effects of hindlimb unweighting (HU) on skeletal muscle anaerobic metabolism were investigated and compared with nonsuspended controls (C). Soleus (SOL), plantaris (PL), and red and white portions of the gastrocnemius (RG, WG) were sampled from resting and stimulated limbs. Muscle atrophy after HU was 46% in SOL, 22% in PL, and 24% in the gastrocnemius compared with nonsuspended C animals. The muscles innervated by the sciatic nerve were stimulated to contract with an occluded circulation for 60 s with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1.0 Hz. Peak tension development by the gastrocnemius-PL-SOL muscle group was similar in HU and C animals (13.0 +/- 1.2, 12.2 +/- 0.8 N/g wet muscle). Occlusion of the circulation before stimulation created a predominantly anaerobic environment, and in situ glycogenolysis and glycolysis were estimated from accumulations of glycolytic intermediates. Total glycogenolysis and glycolysis were higher in the RG muscle of HU animals (74.6 +/- 3.3, 58.1 +/- 1.1) relative to C (57.1 +/- 4.6, 46.1 +/- 2.9 mumol glucosyl units/g dry muscle). Consequently, total anaerobic ATP production was also increased (HU, 251.3 +/- 1.1; C, 204.6 +/- 8.9 mumol ATP/g dry muscle). Total ATP production, glycogenolysis, and glycolysis were unaffected by HU in SOL, PL, and WG muscles. The enhanced glycolytic activity in RG after HU may be attributed to a shift in the metabolic profile from oxidative to glycolytic in the fast oxidative-glycolytic fiber population.     

Effects of hindlimb unweighting and aging on rat semimembranosus muscle and myosin.

We tested the hypothesis that lower specific force (force/cross-sectional area) generated by type II fibers from hindlimb-unweighted rats resulted from structural changes in myosin (i.e., a change in the ratio of myosin cross bridges in the weak- and strong-binding state during contraction). In addition, we determined whether those changes were age dependent. Permeabilized semimembranosus muscle fibers from young adult and aged rats, some of which were hindlimb unweighted for 3 wk, were studied for Ca(2+)-activated force generation and maximal unloaded shortening velocity. Fibers were also spin labeled specifically at myosin Cys707 to assess the structural distribution of myosin during maximal isometric contraction using electron paramagnetic resonance spectroscopy. Myosin heavy chain isoform (MHC) expression and the ratio of MHC to actin were evaluated in each fiber. Fibers from the unweighted rats generated 34% less specific force than fibers from weight-bearing rats (P < 0.001), independent of age. Electron paramagnetic resonance analyses showed that the fraction of myosin heads in the strong-binding structural state during contraction was 11% lower in fibers from the unweighted rats (P = 0.019), independent of age. More fibers from unweighted rats coexpressed MHC IIB-IIX compared with fibers from weight-bearing rats (P = 0.049). Unweighting induced a slowing of maximal unloaded shortening velocity and an increase in the ratio of MHC to actin in fibers from young rats only. These data indicate that altered myosin structural distribution during contraction and a preferential loss of actin contribute to unweighting-induced muscle weakness. Furthermore, the age of the rat has an influence on some parameters of changes in muscle contractility that are induced by unweighting.     

Elevated interstitial fluid volume in rat soleus muscles by hindlimb unweighting.

Hindlimb unweighting is a commonly used model to study skeletal muscle atrophy associated with disuse and exposure to microgravity. However, a discrepancy in findings between single fibers and whole muscle has been observed. In unweighted solei, specific tension deficits are greater in whole muscle than in single fibers. Also, metabolic enzyme activity when normalized per gram of mass is depressed in whole muscle but not in single fibers. These observations suggest that soleus muscle interstitial fluid volume may be elevated with atrophy caused by unweighting in rats. The purpose of this study was to determine if soleus muscle atrophy induced by unweighting is accompanied by alterations in muscle interstitial fluid volume and to calculate the effect of any such alterations on the muscle specific tension (N/cm2 muscle cross-sectional area). Nine female Wistar rats (200 g) were hindlimb unweighted (HU) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147.8 +/- 2.3 mg; HU = 62.3 +/- 3.6 mg, P less than 0.001). Relative muscle interstitial fluid volume increased 107% in HU rats (35.5 +/- 2.8 microliters/100 mg wet mass) compared with the control value of 17.2 +/- 0.5 microliters/100 mg (P less than 0.001); however, absolute interstitial fluid volume (microliters) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta.

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.     

Rat small mesenteric artery function after hindlimb suspension.

To determine whether simulated microgravity in rats is associated with vascular dysfunction, we measured responses of isolated, pressurized mesenteric resistance artery segments (157- to 388-microm ID) to vasoconstrictors, pressure, and shear stress after 28-day hindlimb suspension (HS). Results indicated no differences between HS and control (C) groups in 1) sensitivity or maximal responses to vasoconstrictors (norepinephrine, phenylephrine, serotonin, KCl); 2) ID, external diameter, or ratio of wall thickness to ID; 3) distensibility; or 4) vasodilatory responses to shear stress. Myogenic tone was attenuated (P < 0.05) in HS arteries vs. C, as evidenced by 1) decreased magnitude of tone in larger vessels (second-order branch off superior mesenteric artery, 261- to 388-microm ID) at pressures >/=40 mmHg in the presence of phenylephrine (10(-7) M) and 2) decreased magnitude of tone in smaller vessels (third-order branch off superior mesenteric artery, 157- to 277-microm ID), which exhibited spontaneous tone, at pressures > or =70 mmHg. This attenuation of myogenic tone after HS could contribute to orthostatic intolerance because myogenic tone contributes to the overall tone of resistance arteries.     

Atrophy of the soleus muscle by hindlimb unweighting

The unweighting model is a unique whole animal model that will permit the future delineation of the mechanism(s) by which gravity maintains contractile mass in postural (slow-twitch) skeletal muscle. Since the origination of the model of rodent hindlimb unweighting almost one decade ago, about half of the 59 refereed articles in which this model was utilized have been published in the Journal of Applied Physiology. Thus the purpose of this review is to provide, for those researchers with an interest in the hindlimb unweighting model, a summation of the data derived from this model to data and hopefully to stimulate research interest in aspects of the model for which data are lacking. The stress response of the animal to hindlimb unweighting is transient, minimal in magnitude, and somewhat variable. After 1 wk of unweighting, the animal exhibits no chronic signs of stress. The atrophy of the soleus muscle, a predominantly slow-twitch muscle, is emphasized because unweighting preferentially affects it compared with other calf muscles, which are mainly fast-twitch muscles. The review considers the following information about the unweighted soleus muscle: electromyogram activity, amount and type of protein lost, capillarization, oxidative capacity, glycolytic enzyme activities, fiber cross section, contractile properties, glucose uptake, sensitivity to insulin, protein synthesis and degradation rates, glucocorticoid receptor numbers, responses of specific mRNAs, and changes in metabolite concentrations.     

Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting.

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.     

Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation

The passive and active length-tension relationships of isolated rat mesenteric lymphatics ( approximately 150 microm ID), and adjacent small arteries ( approximately 240 microm) and veins ( approximately 275 microm) were compared under isometric conditions using a wire myograph. About 60% of the lymphatic vessels developed spontaneous contractions in physiological saline solution at nominal preload. To maximally activate smooth muscle, 145 mM K(+) + 5 x 10(-5) M norepinephrine was used for arteries, and 145 mM K(+) + 1 x 10(-6) M substance P was used for lymphatics and veins. In response, arteries exhibited monotonic force development to a plateau level, whereas lymphatics and veins showed biphasic force development, consisting of a transient force peak followed by partial relaxation to a plateau over approximately 5 min. The passive and the active length-tension curves were similar in shape among all three vessels. However, the maximal active tension of arteries (3.4 +/- 0.42 mN/mm) was significantly greater than peak active tension (0.59 +/- 0.04 mN/mm) or plateau tension (0.20 +/- 0.04 mN/mm) in small veins and greater than peak active tension (0.34 +/- 0.02 mN/mm) or plateau tension (0.21 +/- 0.02 mN/mm) in lymphatics. Maximal active medial wall stress was similar between lymphatics and veins but was approximately fivefold higher in small arteries. For lymphatics, the pressure calculated from the optimal preload was significantly higher than that found previously in isobaric studies of isolated lymphatics, suggesting the capacity to operate at higher than normal pressures for increased responsiveness. Our results represent the first mechanical comparisons of arterial, venous, and lymphatic vessels in the same vasculature.     

Regression of capillary network in atrophied soleus muscle induced by hindlimb unweighting.

Little is known about the mechanisms responsible for the adaptation and changes in the capillary network of hindlimb unweighting (HU)-induced atrophied skeletal muscle, especially the coupling between functional and structural alterations of intercapillary anastomoses and tortuosity of capillaries. We hypothesized that muscle atrophy by HU leads to the apoptotic regression of the capillaries and intercapillary anastomoses with their functional alteration in hemodynamics. To clarify the three-dimensional architecture of the capillary network, contrast medium-injected rat soleus muscles were visualized clearly using a confocal laser scanning microscope, and sections were stained by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and with anti-von Willebrand factor. In vivo, the red blood cell velocity of soleus muscle capillaries were determined with a pencil-lens intravital microscope brought into direct contact with the soleus surface. After HU, the total muscle mass, myofibril protein mass, and slow-type myosin heavy chain content were significantly lower. The number of capillaries paralleling muscle fiber and red blood cells velocity were higher in atrophied soleus. However, the mean capillary volume and capillary luminal diameter were significantly smaller after HU than in the age-matched control group. In addition, we found that the number of anastomoses and the tortuosity were significantly lower and TUNEL-positive endothelial cells were observed in atrophied soleus muscles, especially the anastomoses and/or tortuous capillaries. These results indicate that muscle atrophy by HU generates structural alterations in the capillary network, and apoptosis appears to occur in the endothelial cell of the muscle capillaries.     

Analysis of effects of connexin-mimetic peptides in rat mesenteric small arteries

Synthetic peptides homologous to the extracellular loops of the major vascular connexins represent a novel class of gap junction blockers that have been used to assess the role of direct cellular communication in arteries and veins. However, the specificity of action of such peptides on the coupling between smooth muscle cells (SMCs) has not yet been fully characterized. Isolated third-order rat mesenteric arteries were therefore studied with respect to isometric tension (myography), intracellular Ca2+ concentration ([Ca2+]i) (Ca2+ -sensitive dyes), membrane potential, and input resistance (sharp intracellular glass electrodes). Confocal imaging was used for visualization of [Ca2+]i events in individual SMCs in the arterial wall and membrane currents (patch clamp) measured in individual SMCs isolated from the same arteries. A triple peptide combination (37,43Gap 27 + 40Gap 27 + 43Gap 26) increased intercellular resistance (measured as input resistance) in intact arterial segments without affecting the membrane conductance of individual cells and also interrupted electrical coupling between pairs of rat aortic A7r5 myocytes. In intact arterial segments, the peptides desynchronized [Ca2+]i transients in individual SMCs and abolished vasomotion without suppressing Ca2+ transients in individual cells. They also depolarized SMCs, increased [Ca2+]i, and attenuated acetylcholine-induced, endothelium-dependent smooth muscle hyperpolarization. Experiments with endothelium-denuded arteries suggested that the depolarization produced by the peptides under basal conditions was in part secondary to electrical uncoupling of the endothelium from SMCs with loss of a tonic hyperpolarizing effect of the endothelium. Taken together, the results indicate that connexin-mimetic peptides block electrical signaling in rat mesenteric small arteries without exerting major nonjunctional effects.     

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

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 Ca(2+) 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 cmH(2)O. 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 cmH(2)O) 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.     

Characteristics of myogenic reactivity in isolated rat mesenteric veins

Mechanisms of mechanically induced venous tone and its interaction with the endothelium and key vasoactive neurohormones are not well established. We investigated the contribution of the endothelium, l-type voltage-operated calcium channels (L-VOCCs), and PKC and Rho kinase to myogenic reactivity in mesenteric vessels exposed to increasing transmural pressure. The interaction of myogenic reactivity with norepinephrine (NE) and endothelin-1 (ET-1) was also investigated. Pressure myography was used to study isolated, cannulated, third-order rat mesenteric small veins and arteries. NE and ET-1 concentration response curves were constructed at low, intermediate, and high transmural pressures. Myogenic reactivity was not altered by nitric oxide synthase inhibition with N(ω)-nitro-L-arginine (L-NNA; 100 μM) or endothelium removal in both vessels. L-VOCCs blockade (nifedipine, 1 μM) completely abolished arterial tone, while only partially reducing venous tone. PKC (chelerythrine, 2.5 μM) and Rho kinase (Y27632, 3 μM) inhibitors largely abolished venous and arterial myogenic reactivity. There was no significant difference in the sensitivity of NE or ET-1-induced contractions within vessels. However, veins were more sensitive to NE and ET-1 when compared with corresponding arteries at low, intermediate, and high transmural pressures, respectively. These results suggest that 1) myogenic factors are important contributors to net venous tone in mesenteric veins; 2) PKC and Rho activation are important in myogenic reactivity in both vessels, while l-VOCCs play a limited role in the veins vs. the arteries, and the endothelium does not appear to modulate myogenic reactivity in either vessel type; and 3) mesenteric veins maintain an enhanced sensitivity to NE and ET-1 compared with the arteries when studied under conditions of changing transmural distending pressure.     

Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology.

Hindlimb unloading (HU) of rats induces a cephalic shift in body fluids. We hypothesized that the putative increase in cranial fluid pressure and decrease in peripheral fluid pressure would alter the morphology of resistance arteries from 2-wk HU male Sprague-Dawley rats. To test this hypothesis, the cerebral basilar, mesenteric, and splenic arteries were removed from control (C) and HU animals. The vessels were cannulated, and luminal pressure was set to 60 cmH(2)O. The resistance arteries were then relaxed with 10(-4) M nitroprusside, fixed, and cut into transverse cross sections (5 microm thick). Media cross-sectional area (CSA), intraluminal CSA, media layer thickness, vessel outer perimeter, and media nuclei number were determined. In the basilar artery, both media CSA (HU 17, 893 +/- 2,539 microm(2); C 12,904 +/- 1,433 microm(2)) and thickness (HU 33.9 +/- 4.1 microm; C 22.3 +/- 3.2 microm) were increased with hindlimb unloading (P < 0.05), intraluminal CSA decreased (HU 7,816 +/- 3,045 microm(2); C 13,469 +/- 5,500 microm(2)) (P < 0.05), and vessel outer perimeter and media nuclei number were unaltered. There were no differences in mesenteric or splenic resistance artery morphology between HU and C rats. These findings suggest that hindlimb unloading-induced increases in cephalic arterial pressure and, correspondingly, increases in circumferential wall stress result in the hypertrophy of basilar artery smooth muscle cells.     

Age effects on rat hindlimb muscle atrophy during suspension unloading.

Disuse can induce numerous adaptive alterations in skeletal muscle. In the present study the effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450 g) and juvenile (200 g) rats after 1, 7, or 14 days of whole body suspension. Quantitatively and qualitatively the soleus (S), gastrocnemius (G), plantaris (P), and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicated a less rapid rate of response in adult muscles. This was corroborated by assessment of muscle alpha-actin mRNA levels, which indicated a rapid (within 1 day) and significant (P less than 0.05) effect in juveniles but not in adults. The results of this investigation indicate 1) a qualitatively similar differential effect of unloading on muscles of adults and juveniles, 2) a quantitatively reduced and less rapid effect of suspension on adult muscles, and 3) a close similarity of adult and juvenile muscle responses during suspension and spaceflight, suggesting that this ground-based model simulates many of the unloading effects of weightlessness.     

Contractile function of single muscle fibers after hindlimb unweighting in aged rats

Thompson, L. V., and J. A. Shoeman. Contractilefunction of single muscle fibers after hindlimb unweighting in aged rats. J. Appl. Physiol. 84(1):229-235, 1998.This investigation determined how muscle atrophyproduced by hindlimb unweighting (HU) alters the contractile functionof single muscle fibers from older animals (30 mo). After 1 wk of HU,small bundles of fibers were isolated from the soleus muscles and thedeep region of the lateral head of the gastrocnemius muscles. Singleglycerinated fibers were suspended between a motor lever and forcetransducer, functional properties were studied, and the myosin heavychain (MHC) composition was determined electrophoretically. After HU, the diameter of type I MHC fibers of the soleus declined (88 ± 2 vs. 80 ± 4 µm) and reductions were observed in peak active force (47 ± 3 vs. 28 ± 3 mg) and peak specific tension(P_o; 80 ± 5 vs. 56 ± 5 kN/m²). The maximal unloadedshortening velocity increased. The type I MHC fibers from thegastrocnemius showed reductions in diameter (14%), peak active force(41%), and P_o (24%), whereas thetype IIa MHC fibers showed reductions in peak active force andP_o. Thus 1 wk ofinactivity has a significant effect on the force-generating capacity ofsingle skeletal muscle fibers from older animals in a fibertype-specific manner (type I MHC > type IIa MHC > type I-IIa MHC).The decline in the functional properties of single skeletal musclefibers in the older animals appears to be more pronounced than what hasbeen reported in younger animal populations.