Biomedical subjects

S Egginton

Publications and source records attributed to S Egginton.

At least 37 records · Page 2Linked to original sources

PubMed2001

Differential effects of cold exposure on muscle fibre composition and capillary supply in hibernator and non-hibernator rodents.

Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 degrees C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 +/- 0.15, normothermia, N; 1.69 +/- 0.05, hypothermia, H) and average capillary density (CD) (188 +/- 14 mm(-2), N; 201 +/- 12 mm(-2,) H). Similarly, the average C:F was unaltered in hamsters (2.75 +/- 0.11, N; 2.72 +/- 0.15, H), although the 30 % smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 +/- 80 mm(-2) (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 microm2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 microm2, N; 846 microm2, H; n.s.) but a marked reduction in the core (871 microm2, N; 604 microm2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy.

Acclimatization↗

PubMed2001

Relationship between capillary angiogenesis, fiber type, and fiber size in chronic systemic hypoxia.

Whether chronic hypoxia causes angiogenesis in skeletal muscle is controversial. Male Wistar rats, 5--6 wk of age, were kept at constant 12% O(2) for 3 wk, and frozen sections of their postural soleus (SOL), phasic extensor digitorum longus (EDL), and tibialis anterior (TA) muscles were compared with those of normoxic controls. Capillary supply increased in SOL muscles [capillary-to-fiber ratio (C/F) = 2.55 +/- 0.09 hypoxia vs. 2.17 +/- 0.06 normoxia; capillary density (CD) = 942 +/- 14 hypoxia vs. 832 +/- 20 mm(-2) normoxia, P < 0.01] but not in EDL muscles (C/F = 1.44 +/- 0.04 hypoxia vs. 1.42 +/- 0.04 normoxia; CD = 876 +/- 52 hypoxia vs. 896 +/- 24 mm(-2) normoxia). The predominantly glycolytic cortex of TA muscles showed higher C/F after hypoxia (1.79 +/- 0.09 vs. 1.53 +/- 0.05 normoxia, P < 0.05), whereas the mainly oxidative TA core with smaller fibers showed no change in capillarity. The region of the SOL muscle with large-sized (mean fiber area 2,843 +/- 128 microm(2)) oxidative fibers (90% type I) had a higher C/F (by 30%) and CD (by 25%), whereas there was no angiogenesis in the region with sparse (76%) and smaller-sized (2,200 +/- 85 microm(2)) type I fibers. Thus systemic hypoxia differentially induces angiogenesis between and within hindlimb skeletal muscles, with fiber size contributing either directly (via a metabolic stimulus) or indirectly (via a mechanical stimulus) to the process.

Animals↗

PubMed2001

Control of vascular tone in notothenioid fishes is determined by phylogeny, not environmental temperature.

We examined potential vasomotor control mechanisms in an Antarctic fish (Trematomus bernacchii; usual core temperature approximately -1 degrees C), comparing sensitivity to agonists by means of the cumulative dose response and potency with reference to depolarization by 50 mM KCl. In efferent branchial arteries, norepinephrine (NE) produced approximately 20% of the maximal KCl tension and ~40% in the presence of 10(-3)M sotalol, suggesting a modest contribution of alpha- and beta-adrenergic tonus [half-maximal response (pEC(50)) = 6.29 +/- 0.37 M]. Carbachol (CBC) and serotonin (5-HT) had different sensitivities (pEC(50) = 4.50 +/- 0.40 and 6.82 +/- 0.08 M, respectively) but similar potencies (21.6 +/- 11.1 and 31.1 +/- 5.3% of KCl). A related species from warmer waters around New Zealand, Paranotothenia angustata, had similar vascular reactivity for NE (pEC(50) = 5.48 +/- 0.31 M), CBC (pEC(50) = 4.94 +/- 0.22 M), and methysergide-sensitive vasoconstriction with 5-HT (pEC(50) = 6.22 +/- 0.40 M). Agonist potencies were 9, 65, and 45% that of KCl, respectively. Bovichtus variegatus, a member of the phylogenetic sister group to the notothenioids, also gave broadly similar responses. In contrast, Dissostichus mawsoni, a pelagic Antarctic notothenioid, showed a dominance of vasodilatation over vasoconstriction, with sensitive isoprenaline (pEC(50) = 6.66 +/- 0.05 M) but weak serotonergic (5.2 +/- 1.5% KCl) responses. The unusual dominance of serotonergic control appears to be primarily a consequence of evolutionary lineage rather than low environmental temperature, but the pattern may be modified according to functional demand.

Animals↗

PubMed2000

The role of pericytes in controlling angiogenesis in vivo.

In order to evaluate the interaction between endothelial cells and the perivascular pericytes during physiological angiogenesis, stereological analysis of fine structure was performed on samples of rat skeletal muscle where capillary growth was induced to a similar extent by three different interventions (indirect electrical stimulation, vasodilatation by alpha 1-blockade, stretch due to synergist extirpation). There was a significant reduction in the relative area of contact between pericytes and the capillary abluminal surface with stimulation, and withdrawal of pericyte processes coincided with an increase in anatomical capillary supply. These data indicate that pericytes may play an anti-angiogenic role in vivo in normal adult tissue similar to that proposed for in vitro models of angiogenesis, with their retraction during increased muscle activity possibly releasing endothelial cells from their contact inhibition. However, following long-term peripheral vasodilatation expansion of the capillary bed was accompanied by a co-ordinated increase in pericytes, such that coverage of capillaries was similar to that in control muscles. In addition, growth of capillaries following prolonged stretch resulted in a slightly greater increase in the pericyte population, suggesting they may be permissive for endothelial cell migration. Thus, the role of pericytes in controlling physiological angiogenesis is dependent on the nature of the initial stimulus, suggesting that in vitro data have to be interpreted with caution when discussing the mechanism of capillary growth in vivo.

Animals↗

PubMed2000

Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle.

Proteolysis of the capillary basement membrane is a hallmark of inflammation-mediated angiogenesis, but it is undetermined whether proteolysis plays a critical role in the process of activity-induced angiogenesis. Matrix metalloproteinases (MMPs) constitute the major class of proteases responsible for degradation of basement membrane proteins. We observed significant elevations of mRNA and protein levels of both MMP-2 and membrane type 1 (MT1)-MMP (2.9 +/- 0.7- and 1.5 +/- 0.1-fold above control, respectively) after 3 days of chronic electrical stimulation of rat skeletal muscle. Inhibition of MMP activity via the inhibitor GM-6001 prevented the growth of new capillaries as assessed by the capillary-to-fiber ratio (1.34 +/- 0.08 in GM-6001-treated muscles compared with 1.69 +/- 0.03 in control 7-day-stimulated muscles). This inhibition correlated with a significant reduction in the number of capillaries with observable breaks in the basement membrane, as assessed by electron microscopy (0.27 +/- 0.27% in GM-6001-treated muscles compared with 3.72 +/- 0.65% in control stimulated muscles). Proliferation of capillary-associated cells was significantly elevated by 2 days and remained elevated throughout 14 days of stimulation. Capillary-associated cell proliferation during muscle stimulation was not affected by MMP inhibition (80.3 +/- 9.3 nuclei in control and 63.5 +/- 8.5 nuclei in GM-6001-treated animals). We conclude that MMP proteolysis of capillary basement membrane proteins is a critical component of physiological angiogenesis, and we postulate that capillary-associated proliferation precedes and occurs independently of endothelial cell sprout formation.

Animals↗

PubMed2000

Thermal compensation of peripheral oxygen transport in skeletal muscle of seasonally acclimatized trout.

Seasonal changes in ultrastructure of locomotory muscle were quantified after acclimatization to natural temperature and photoperiod. Only modest changes were seen in the volume density (V(v)) of mitochondria in slow fibers ranging from 0.21 +/- 0.01 (summer) to 0.24 +/- 0.01 (winter), despite an increase in fiber size from 945 +/- 19 to 1,594 +/- 46 microm(2), respectively, resulting in a significantly greater total mitochondrial volume at low temperatures. In contrast, intracellular lipid stores showed a marked change with season, from a maximum V(v) of lipid droplets of 0.16 +/- 0.01 in winter, progressively declining through spring and summer to a minimum of 0.07 +/- 0.01 in autumn. For both organelles, the surface density reflected changes in V(v), indicating little modification of structure. Seasonal effects may dominate those of environmental temperature on mitochondrial separation, which in winter and spring fish at 4(o)C averaged 0.64 +/- 0.06 and 1.20 +/- 0.07 microm, respectively. The extracellular transport of oxygen also varies with season, the peak capillary density in autumn (2,851 +/- 88 mm(-2)) resulting in a minimum tissue supply (domain) area of 529 +/- 9 microm(2) per capillary. As a consequence, the predicted intracellular PO(2) ( approximately 2.5 kPa) is similar throughout the year.

Acclimatization↗

PubMed2000

Selective long-term electrical stimulation of fast glycolytic fibres increases capillary supply but not oxidative enzyme activity in rat skeletal muscles.

Glycolytic fibres in rat extensor digitorum longus (EDL) and tibialis anterior (TA) were selectively activated, as demonstrated by glycogen depletion, by indirect electrical stimulation via electrodes implanted in the vicinity of the peroneal nerve using high frequency (40 Hz) trains (250 ms at 1 Hz) and low voltage (threshold of palpable contractions). This regime was applied 10 times per day, each bout being of 15 min duration with 60 min recovery, for 2 weeks. Cryostat sections of muscles were stained for alkaline phosphatase to depict capillaries, succinate dehydrogenase (SDH) to demonstrate oxidative fibres, and periodic acid-Schiff reagent (PAS) to verify glycogen depletion. Specific activity of hexokinase (HK), 6-phosphofructokinase, pyruvate kinase, glycogen phosphorylase and cytochrome c oxidase (COX) were estimated separately in homogenates of the EDL and the predominantly glycolytic cortex and oxidative core of the TA. Stimulation increased the activity of HK but not that of oxidative enzymes in fast muscles. Comparison of changes in oxidative capacity and capillary supply showed a dissociation in the predominantly glycolytic TA cortex. Here, COX was 3.9+/-0.68 microM min(-1) (g wet wt)-1 in stimulated muscles compared with 3.7+/-0.52 microM min(-1) (g wet wt)-1 in contralateral muscles (difference not significant), while the percentage of oxidative fibres (those positively stained for SDH) was also similar in stimulated (14.0+/-2.8 %) and contralateral (12.2 +/-1.9 %) muscles. In contrast, the capillary to fibre ratio was significantly increased (2.01+/-0.12 vs. 1.55+/-0.04, P<0.01). We conclude that capillary supply can be increased independently of oxidative capacity, possibly due to haemodynamic factors, and serves metabolite removal to a greater extent than substrate delivery.

Animals↗

PubMed1999

Early changes in performance, blood flow and capillary fine structure in rat fast muscles induced by electrical stimulation.

1. Muscle blood flow, capillary fine structure and performance were investigated in the early stages of chronic indirect electrical stimulation of ankle flexors in the rat. 2. The fast muscles tibialis anterior (TA), extensor digitorum longus (EDL) and extensor hallucis proprius (EHP) were unilaterally stimulated via the right common peroneal nerve at 10 Hz and supramaximal voltage for 8 h a day for 2, 3 or 7 days and compared with muscles from control animals. 3. Muscle blood flow (MBF) was estimated at rest and during contractions by radioactive microspheres. It was higher at rest than in unstimulated controls only in muscles stimulated for 2 days; during contractions it was higher in some muscles stimulated for 3 days than in controls, and in all muscles by 7 days (192 +/- 17 vs. 149 +/- 12 ml (100 g)-1min-1 in controls). 4. Electron microscopical evaluation of individual capillaries in EHP fixed by superfusion in situ revealed thickening of capillary endothelium and decreased lumen volume in muscles stimulated for 7 (P < 0.005) but not 3 days. Significantly smaller capillary size indicates the presence of newly formed capillaries. 5. Isometric twitch tension, recorded from combined TA and EDL in stimulated and contralateral legs during 5 min contractions at 4 Hz, gradually declined from 175 +/- 9 to 99 +/- 4 kN m-2 after 7 days of stimulation (P < 0.05) while the fatigue index, calculated as (final twitch tension/peak twitch tension) x 100, increased from 69.8 +/- 3.4 to 90 +/- 3.0 % (P < 0. 05). No significant changes in the fatigue index occurred in muscles stimulated for 2 or 3 days. 6. Lower peak tension, but not fatigue index or MBF, was also observed in muscles contralateral to those stimulated for 3 and 7 days, which thus do not represent appropriate controls. 7. We conclude that the high resting blood flow found in muscles stimulated for 2 days may initiate the capillary growth reported previously, while the relatively modest increase in MBF during contractions in muscles that had been stimulated for 7 days may be due to increased capillary supply. Swelling of the capillary endothelium and decreased volume of the capillary lumen may result in an increased proportion of time spent by red blood cells in capillaries, which would improve oxygen extraction.

Animals↗

PubMed1999

Antarctic fishes have a limited capacity for catecholamine synthesis.

To determine whether an attenuated stress response is a general feature of Antarctic fish or is dependent on ecotype, the capacity for catecholamine synthesis within the head kidney and plasma levels of the primary stress hormones (catecholamines and cortisol) were determined in species with a range of activity patterns. Tyrosine hydroxylase (TH) activities were similar in both sluggish (Gobionotothen gibberifons, 153+/-22 nmol g(-)(1 )h(-)(1), mean +/- s.e.m.) and active (Notothenia rossii, 185+/-39 nmol g(-)(1 )h(-)(1), Dissostichus mawsoni, 128+/-31 nmol g(-)(1 )h(-)(1)) pelagic nototheniids, but only 30 % of those in Atlantic cod (Gadus morhua, 393+/-88 nmol g(-)(1 )h(-)(1)) at the same temperature. TH activities were even lower in white-blooded channichthyids (Chaenocephalus aceratus, 74+/-16 nmol g(-)(1 )h(-)(1) and Champsocephalus gunnari, 53+/-17 nmol g(-)(1 )h(-)(1)), although values in Chionodraco rastrospinosus were similar to red-blooded species (178+/-45 nmol g(-)(1 )h(-)(1)). Circulating catecholamine levels were extremely high in all species after fishing stress, with adrenaline levels 3-4 times higher than noradrenaline levels. Cortisol levels remained low, ranging from 1.33+/-0.58 ng ml(-)(1) in Champsocephalus gunnari to 44.9+/-25.0 ng ml(-)(1 )in Dissostichus mawsoni. These data suggest that depressed catecholamine synthesis is typical of Antarctic fish regardless of life style, although they are able to release extensive stores from the chromaffin tissue under conditions of extreme trauma. Cortisol does not appear to be an important primary stress hormone in these species.

Animals↗

PubMed1999

Development of the fluorescent microsphere technique for quantifying regional blood flow in small mammals.

We have demonstrated that the fluorescent microsphere technique can be used in small mammals for accurate determination of regional blood flows. In particular we have shown that 100% recovery of trapped microspheres is possible, that tissue digestion can be completed in a shorter time than previously reported, and the error-prone filtration method can be replaced with one of sedimentation. The method gave very good agreement among different fluorescent labels (r2 > 0.99) and low variability among tissues (mean coefficient of variation = 0.06). Simultaneous injection of radiolabelled and fluorescent microspheres established comparability between these methods (r2 = 0.96) for blood flows measured at rest, during vasodilator-induced hypotension, and in muscle hyperaemia during indirect electrical stimulation. Fluorescent microspheres can therefore replace radioactive microspheres for the determination of blood flow with advantages in both safety and cost, without loss of sensitivity.

Animals↗

PubMed1999

The effect of stimulation frequency on blood flow in rat fast skeletal muscles.

The effect of stimulation frequency on intact muscle blood flow was measured by radiolabelled microsphere entrapment. Maximum flow occurred at 4 Hz in both extensor digitorum longus and tibialis anterior (156 +/- 13 and 205 +/- 24 ml min-1 (100 g)-1, respectively). Regional differences in fibre composition were reflected in the relative flow rates, with functional hyperaemia in the oxidative tibialis anterior core being twice that of the glycolytic cortex at 10 Hz. A consistent difference in flow between legs was noted that may originate from an unequal division of the common iliac artery in rats.

Animals↗

PubMed1998

Capillary growth in overloaded, hypertrophic adult rat skeletal muscle: an ultrastructural study.

We examined the early stages of angiogenesis in overloaded m. extensor digitorum longus following extirpation of the agonist m. tibialis anterior. Capillary-to-fibre ratio increased after 1 week (1.54+/-0.02) vs. control (1.38+/0.06; P < 0.01) and resulted in a greater tortuosity of the capillary bed at 2 weeks, indicating the presence of lateral sprouts or anastomoses. Capillary endothelial cells (ECs) showed ultrastructural signs of activation, were thickened, and had irregular luminal and abluminal surfaces. The proportion of ECs with abluminal processes increased after overload (13.5+/-0.6% vs. 2.0+/-1.5%, 1 week vs. contralateral, P < 0.01; 12.5+/-2.6% vs. 3.5+/-0.6%, 2 weeks vs. contralateral, P < 0.01), whereas there was no significant change in proportion of luminal processes. Abluminal processes occurred in approximately 13% of capillaries in overloaded muscles (P < 0.01 v. control and contralateral), and most were associated with focal breakage of the basement membrane (BM). Small sprouts (<3 microm in diameter) comprised of one or two ECs sometimes lacked a lumen, and others had a slitlike or vacuolelike lumen between adjacent ECs or vacuolelike lumen formed by fusion of vesicles within a single EC. Endothelial mitosis was occasionally seen in nonsprouting capillaries with intact BM, increasing the average number of ECs per capillary from approximately 1.7 in control muscles to 2.1 after 1 week of overload (P < 0.05) when bromodeoxyuridine incorporation was also higher (P < 0.001). We conclude that muscle overload induces capillary growth by sprouting of existing capillaries, probably due to mechanical stretch acting from the abluminal side of the vessels.

Animals↗

PubMed1998

Internal division of capillaries in rat skeletal muscle in response to chronic vasodilator treatment with alpha1-antagonist prazosin.

Chronic vasodilatation represents a stimulus for capillary growth associated with increased luminal shear stress. We have examined the ultrastructure of more than 2000 capillaries to establish whether the sequence of angiogenesis in response to this stimulus is similar to that described during development and under pathological circumstances. Administration of the alpha1-blocker prazosin to rats for 2 weeks led to a greater capillary length density in extensor hallucis proprius muscles without any change in capillary tortuosity: Jv(c,f)=262+/-54 compared with 350+/-17 mm-2, control compared with prazosin (P<0.002). There were obvious signs of endothelial cell (EC) activation after prazosin treatment, including an increased proportion of capillaries with rough endoplasmic reticulum, large cytoplasmic vacuoles, thickened endothelium and an irregular luminal surface. Capillaries from control muscles had a maximum of three ECs in cross section, whereas four ECs were noted in 0.8+0.5% of capillaries after 1 week (n.s.) and 2.5+/-0.9% after 2 weeks (P<0.01) of treatment. This could be due to elongation and/or migration of ECs, as cell proliferation has not been described at these time points. There was also an increase in the proportion of capillaries having a narrow, slit-like lumen (1.7+/-0. 8% of controls; 7.1+/-1.9% at 1 week; 8.8+/-2.5% at 2 weeks; P<0.02), some of which were smaller in size (less than 2 microm diameter) than in controls (3-5 microm) and/or "seamless", i.e. lacking EC junctions. These may represent newly formed vessels. Focal discontinuity of the basement membrane and abluminal EC processes were rarely seen, and capillary growth by abluminal sprouting appeared to be very infrequent (less than 0.001% of profiles). Of more importance was growth starting from the luminal side. Significantly more thin cytoplasmic processes were observed protruding into the lumen of capillaries after 1 week (47.5+/-6.2%, P<0.001) and 2 weeks of prazosin (34.2+/-5.5%, P<0.05) than in control vessels (16.7+/-3.9%). Some of these traversed the entire lumen and connected with endothelium of the opposite side, probably involving membrane fusion, resulting in the appearance of a double lumen. Individual capillaries with a complete double lumen were observed after 2 weeks' prazosin but comparatively rarely, in only four out of six muscles. These findings indicate a pattern of luminal growth which is completely different from intussusceptive growth previously described during development, and from the abluminal capillary sprouting seen under pathological circumstances.

Adrenergic alpha-Antagonists↗

PubMed1998

Lack of involvement of basic fibroblast growth factor (FGF-2) in capillary growth in skeletal muscles exposed to long-term contractile activity.

Fibroblast growth factors (FGFs) are involved in stimulation of angiogenesis in tumors and other pathological circumstances. Increased activity of normal skeletal muscles resulting from chronic electrical stimulation is a very potent stimulus for capillary growth but a relationship between the initiation of this angiogenesis and the involvement of autocrine growth factors has yet to be established. Although FGF expression has been reported in muscles stimulated for 3 weeks, capillary growth is underway significantly earlier, beginning around 3 days. The present experiments have therefore studied the possible involvement of basic fibroblast growth factor (FGF-2) in stimulated rat fast skeletal muscles prior to, and coincident with, capillary growth. Muscle contractions were induced via electrodes implanted in the vicinity of the peroneal nerve and maintained for 8h/day for 2, 4 or 7 days. Capillary/fiber ratio (C/F), based on staining of capillary endothelium for alkaline phosphatase, was not changed in either extensor digitorum longus (EDL) or tibialis anterior (TA) after 2 days stimulation, but increased in TA stimulated for 4 days and in both muscles after 7 days. The expression of mRNA for FGF-2, detected by ribonuclease protection assay, was decreased in all stimulated muscles compared with control or contralateral muscles; immunohistochemistry showed FGF-2 gene product in nerves and larger blood vessels but not in capillaries. There was no evidence from immunohistochemistry for up-regulation of receptors flg and bek for FGF-2. The presence of FGF-2, flg and bek in arterioles may indicate a possible role for FGF-2 in the regulation of blood flow since we have previously shown it to be a dilator of small arterioles. However, based on the lack of correlation between changes in capillary density and the expression of mRNA and protein for FGF-2 and its receptors, it is unlikely that it is directly linked with the initiation of angiogenesis resulting from chronic activity in skeletal muscles.

Journal Article↗

PubMed1998

Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle.

Rat extensor digitorum longus muscles were overloaded by stretch after removal of the synergist tibialis anterior muscle to determine the relationship between capillary growth, muscle blood flow, and presence of growth factors. After 2 wk, sarcomere length increased from 2.4 to 2.9 micrometers. Capillary-to-fiber ratio, estimated from alkaline phosphatase-stained frozen sections, was increased by 33% (P < 0.0001) and 60% (P < 0.01), compared with control muscles (1.44 +/- 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with any changes in mRNA for basic fibroblast growth factor (FGF-2) or its protein distribution. FGF-2 immunoreactivity was present in nerves and large blood vessels but was negative in capillaries, whereas the activity of low-molecular endothelial-cell-stimulating angiogenic factor (ESAF) was 50% higher in stretched muscles. Muscle blood flows measured by radiolabeled microspheres during contractions were not significantly different after 2 or 8 wk (132 +/- 37 and 177 +/- 22 ml. min-1. 100 g-1, respectively) from weight-matched controls (156 +/- 12 and 150 +/- 10 ml. min-1. 100 g-1, respectively). Resistance to fatigue during 5-min isometric contractions (final/peak tension x 100) was similar in 2-wk overloaded and contralateral muscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with 77% in contralateral muscles and 67% in controls. We conclude that increased blood flow cannot be responsible for initiating expansion of the capillary bed, nor does it explain the reduced fatigue within overloaded muscles. However, stretch can present a mechanical stimulus to capillary growth, acting either directly on the capillary abluminal surface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.

Animals↗

PubMed1998

Growth of arterioles in chronically stimulated adult rat skeletal muscle.

OBJECTIVE: The purpose of this study was to test the hypothesis that capillary growth induced by chronic electrical stimulation of skeletal muscle is accompanied by the growth of small arterioles. METHODS: Lower limb flexor muscles of Sprague-Dawley rats were stimulated by electrodes implanted in the vicinity of the peroneal nerve at 10 Hz for 8 h/d for 2 and 7 days. Cryostat sections from the proximal, middle, and distal regions of the extensor digitorum longus muscle (EDL) were fluorescently immunolabeled with alpha-smooth muscle actin (alpha SMA) and myosin heavy chain (MHC) to identify mature (alpha SMA and MHC-positive) and immature (alpha SMA-positive, MHC-negative) arterioles. The fluorescent derivative of the lectin Griffonia simplicifolia I (GSI) was used to identify all microvessels, including arterioles, capillaries, and venules. RESULTS: The number of vessels positive for GSI or alpha SMA surrounding muscle fibers was similar in all three muscle regions (proximal, middle, distal). The mean values +/- SEM for GSI-positive vessels from all regions were similar in control (4.3 +/- 0.07) and 2-day stimulated (4.7 +/- 0.08) but higher in 7-day stimulated muscles (6.7 +/- 0.1, p < 0.05), thus confirming the previous findings on capillary growth. A similar increase was found in the number of alpha SMA positive vessels < or = 10 microns outer diameter (1.3 +/- 0.09 versus 0.4 +/- 0.03 around muscle fibers in controls). The density of terminal arterioles (< or = 10 microns) was slightly but not significantly higher after 2 days of stimulation (19.5 +/- 4 versus 15.6 +/- 2 profiles/mm2 in control muscles) and significantly higher after 7 days (33 +/- 7). While a similar increase was observed in the density of preterminal arterioles > 10 microns (17 +/- 3 control, 22 +/- 3 at 2 days and 40 +/- 5 at 7 days), the density of MHC-positive vessels muscles stimulated for 7 days was unchanged. Seven-day stimulated muscle also had a fivefold higher density of microvessel profiles < or = 10 microns that were only partially surrounded by alpha SMA. This considerably exceeds the relative increase in the number of capillaries and thus supports the concept of arteriolar growth by transformation from capillaries. CONCLUSIONS: Chronic electrical stimulation results in an early increase in the number of immature (MHG-negative), but not mature (MHC-positive) arterioles, a process that accompanies the increase in capillarization. The great increase in the number of microvessels only partially covered by alpha SMA suggests arteriolization of capillaries as a contributing mechanism in this growth.

Actins↗

PubMed1997

The possible role of intracellular lipid in determining oxygen delivery to fish skeletal muscle.

Transcellular oxygen flux in skeletal muscle fibres was modelled mathematically. In eels at the same environmental temperature (15 degrees C), changes in muscle structure associated with increased levels of activity elevated mean fibre Po2 by 30% to 5.2 kPa, despite greater fibre radius and Vo2, due to more capillaries and intracellular lipid. The latter results in a 68% increase in oxygen permeability ([symbol: see text]o2). While cold acclimation of striped bass (5 vs. 25 degrees C) led to a modest (12%) fibre hypertrophy, Vo2 fell proportionately more (by 60%). A 50% increase in capillary supply again aids oxygen flux, while the presence of intracellular lipid effectively reverses the cold-induced decrease in [symbol: see text]o2. The combined effect is to increase mean fibre Po2 from 1.9 to 4.6 kPa and minimum Po2 from 0.57 to 4.2 kPa, respectively. These data suggest little selection pressure exists to alter fibre composition in order to increase peripheral oxygen transport, while the magnitude of change in intracellular Po2 is likely in excess of that required to maintain locomotory activity. Hence, there may be some other factor than Po2 regulating structural reorganisation of muscle fine structure.

Anguilla↗

PubMed1997

Is human skeletal muscle capillary supply modelled according to fibre size or fibre type?

Analysis of muscle supply usually relies on estimating either the numerical capillary to fibre ratio or capillary density. Both indices are scale dependent, i.e. they vary with fibre size. We have examined the use of an alternative approach based on the anatomical supply area of individual capillaries, which allows the calculation of a local capillary to fibre ration or density based on area, rather than number of fibres. The results suggest that, in human skeletal muscle, capillary supply is primarily scaled according to fibre size, and is relatively independent of fibre type.

Adult↗