This Article Abstract Full Text (PDF) Services Download to citation manager PubMed PubMed Citation

Arteriolar and Venular Capillary Distribution in Skeletal Muscles of Old Rats

Department of Medicine, University of California, San Diego, La Jolla.

Address correspondence to Mark Olfert, PhD, Department of Medicine, 0623A, University of California, San Diego, La Jolla, CA 92093-0623. E-mail: molfert{at}ucsd.edu

	Abstract

Top Abstract Methods Results Discussion References

 
Decreased skeletal muscle mass and proportion of fast-twitch glycolytic fibers are well-documented correlates of aging; however, data on concomitant changes on capillary-to-fiber ratio (C:F) are inconsistent. We simultaneously examined fiber-type composition and arteriolar and venular portions of capillaries in the distal hind-limb muscles of 12-, 24-, and 35-month old F1 hybrid F344 Brown Norway rats. Aging significantly increased C:F of venular capillaries in muscles, which also presented significant age-related increase in slow-(type I) and fast-(type IIa) oxidative fibers (plantaris, tibialis anterior, medial gastrocnemius; p <.05). In contrast, arteriolar and venular capillary proportions did not change in the soleus, extensor digitorum longus, or lateral gastrocnemius. These data suggest that age-associated increases in skeletal muscle capillarity may be due to the venular portion of capillaries and that the increase occurs primarily in muscles that demonstrate increased oxidative potential with age.

Key Words: Fiber type • Capillary density • Capillary-to-fiber ratio • Skeletal muscle • Morphometry

Studies in both humans and animals have also produced conflicting results in skeletal muscle capillarity, with results showing increases (22,23), decreases (24–27), or no change (28–34) in muscle capillaries with advancing age. Given the increasing recognition that angiogenesis is important in both health and disease, deciphering the parameters and/or conditions regulating age-associated changes in skeletal muscle capillarity is vitally important before we can fully appreciate the underlying regulatory mechanism(s) involved. In recent years, there has been growing interest in the differential regulation (and/or dysregulation) of arteriolar versus venular portion of capillaries. In most organs, the phenotype of endothelial cells is different in arterioles and venules [see review (35)]. For example, whereas venules are capable of leaking plasma and have been shown to be responsive to inflammatory mediators, such as histamine, bradykinin, and serotonin, these responses are not seen in arterioles. Endothelial cell differences also appear to extend to arteriolar and venular portions of capillaries, for example, sprouting of capillaries during wound healing is reported to occur primarily from the venule side of capillaries (36). Evidence of differential regulation of angiogenesis between arteriolar and venular capillary segments is also supported by a recent study using transgenic mice selectively expressing single isoforms of vascular endothelial growth factor: VEGF^120/120, VEGF^164/164, or VEGF^188/188 (37). In that study, retinal angiogenesis was normal in mice that expressed only the VEGF^164/164 isoform, whereas mice that expressed only the VEGF^188/188 isoform had impaired arteriolar capillary development but normal venular capillary growth (37). These data provide a potential mechanism for differential arteriolar and venular capillary regulation and lend support to the notion that arteriolar and venular capillary segments can be differentially altered. Interestingly, these data may also, in part, provide an explanation for differential venular and arteriolar capillary density responses that have recently been recognized following exercise training (38,39) and chronic muscle stimulation (40).

Given the conflicting studies on age-related changes in muscle capillarity and fiber-type composition, we sought to determine the impact of age on the proportion of arteriolar and venular capillary segments in relation to fiber-type composition. We chose to use the F1 hybrid Fischer 344 x Brown Norway (F344BN) rat for this study due to its increased longevity (mean life expectancy, 40 months) and lower incidence of major pathologies with advanced age compared to other strains (41). We examined several hind-limb muscles and muscle regions to exploit the expected variability in fiber-type distribution, as well as the suspected variability in age-related changes in the muscle. The soleus (SOL) muscle represented the most aerobic muscle (highest % type I fibers), whereas the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles represented the least aerobic muscle (highest % type IIb fibers). Muscles with more mixed fiber-type composition, such as the medial and lateral gastrocnemius (GM and GL) and plantaris (PL), were also studied. We hypothesized that differential age-related changes in skeletal muscle capillarity may be related to the distribution of arteriolar and venular capillary segments and that this may be linked to specific fiber-type profile with advancing age, such that greater arteriolar capillaries would be expected in muscles with greater aerobic fibers.

	METHODS

Top Abstract Methods Results Discussion References

 
Animals
Twenty-six male F344BN rats were obtained from the National Institute on Aging at 12 (n = 9), 24 (n = 10), and 35 months of age (n = 7). Rats were received 1–3 weeks prior to the study and housed in standard size rodent cages with 2–3 rats per cage. They were maintained on 12-hour light/dark cycles and fed standard rat chow (Harlan Teklad 8604; Madison, WI) with untreated tap water ad libitum. The study was approved by the Institutional Animal Care and Use Committee and conducted in pathogen-free facilities accredited by the American Association of Accreditation of Laboratory Animal Care.

Tissue Preparation
At the time of tissue collection, body mass averaged 449 ± 15 g (n = 9), 505 ± 14 g (n = 10), and 519 ± 19 g (n = 7) in the 12-, 24-, and 35-month-old rats, respectively. All rats were anesthetized by intraperitoneal injection of sodium pentobarbital (40–125 mg/kg), and TA, EDL, SOL, PL, GM, and GL muscles were dissected from both right and left hind limbs and individually weighed. Only the right hind limb was used for data analysis in this study. Each muscle was sampled at mid-belly, and 3-mm-thick entire cross-sections were mounted on cork disks with tissue-freezing medium (TFM; Triangle Biomedical Sciences, Durham, NC) and frozen in isopentane cooled to –140°C in liquid nitrogen. All samples were stored at –80°C until sectioning. Eight-micrometer-thick serial transverse sections (7–10 per muscle sample) were cut at –20°C on a cryostat (Jung-Reichert Cryocut 1800; Cambridge Instruments, Germany) and kept at –20°C until histochemical processing.

Capillary Staining
Sections were stained for dipeptidyl peptidase IV (DPP IV) and alkaline phosphatase (AP) activity following the method of Lodja (42), as applied to skeletal muscle tissue by Mrazkova and colleagues (43). DDP IV is highly expressed in the venular portion of the capillary, whereas AP is selectively expressed in the arteriolar portion of the capillary, thus allowing differentiation between venular and arteriolar segments. Briefly, sections were immersed in a cooled acetone–chloroform (1:1) mixture for 5 minutes, before being placed in the DPP and following AP reaction mixtures. DPP IV (venular portion of capillary, stained red) was detected via an Azo coupling procedure with glycyl-prolyl-4-methoxy-β-naphthylamide hydrochloride (Sigma, St. Louis, MO) and O-Dianisidine-tetrazotized (Fast Blue B Salt; Sigma) in sodium phosphate buffer at pH 7.2–7.4. Sections were incubated at 37°C for 30–60 minutes. For detection of AP (arteriolar portion of capillary, stained blue), naphthol AS-MX phosphate (3-hydroxy-2-naphthoic acid 2,4-dimethylanylide; Sigma) and 4-amino-diphenylamine diazonium sulfate variance blue salt (Sigma) were used in Tris-HCl buffer at pH 9.0–9.2. Sections were incubated for 30–60 minutes at 37°C.

Fiber Typing
Adjacent sections were stained by the metachromatic dye-ATPase method described by Ogilvie and Feeback (44) to simultaneously identify fiber types in single sections. Briefly, the sections were first preincubated in potassium acetate and calcium chloride for 8 minutes at room temperature, followed by incubation in ATPase staining medium (44) at room temperature for 30 minutes, and stained with toluidine blue. This procedure stains type I skeletal muscle fibers turquoise to dark blue with a darker border, type IIA light blue, and type IIB intermediate blue to violet. Serial sections were also stained by classic myofibrillar ATPase staining using acid and alkaline preincubations (45,46), to verify fiber-type identification in each muscle and age group.

Morphometry
All analyses were performed by a single observer blinded to the identity of the samples. Measurements were carried out by point-counting using a 100-point eyepiece square grid on sections examined at a magnification of x250 with a light microscope. A minimum of 8 and maximum of 27 fields (from one section) were randomly selected by systematic random sampling and were used to estimate the relative cross-sectional area and number of type I, IIA, and IIB fibers in metachromatically stained sections, resulting in an average of 10 ± 1 (standard deviation [SD]) fields for each DPP IV-stained and AP-stained section and an average of 761 ± 162 (SD) fiber profiles examined per muscle.

Statistical Analyses
All data are reported as mean ± standard error, unless otherwise indicated. Group means were compared by analysis of variance (ANOVA). One-way ANOVA was used to compare body mass between age groups (12-, 24-, and 35-months). Two-way ANOVA was used to test for differences among age groups and muscles, and for interaction between group and muscle with Holm–Sidak multiple comparison post hoc tests (SigmaStat 3.1; SPSS, Chicago, IL). Significance was defined as p <.05.

	RESULTS

Top Abstract Methods Results Discussion References

 
Skeletal Muscle Mass and Fiber Cross-Sectional Area
The weight of all six muscles decreased significantly from 12 to 35 months of age, with the greatest relative loss (44%) observed in GL, and the least (22%) in EDL (Figure 1A). The average fiber cross-sectional area also decreased significantly in each muscle from 12- and 35- months of age (Figure 1B), again with the largest decline in 43% (EDL) and the smallest decline in 22% (PL).

View larger version (17K): [in this window] [in a new window]   Figure 1. Decreased muscle weight (A) and average fiber cross-sectional areas (B) in soleus (SOL), extensor digitorum longus (EDL), lateral gastrocnemius (GL), plantaris (PL), tibialis antierior (TA), and medial gastrocnemius (GM) muscles in 12-, 24-, and 35-month old F1 hybrid F344BN rats. *Significantly different compared with 12-month old rats, p <.05

View larger version (16K): [in this window] [in a new window]   Figure 2. Effect of aging on the proportion (%) of the relative cross-sectional areas of (A) type I, (B) type IIa, and (C) type IIb muscle fibers to the cross-sectional area of total muscle fibers in soleus (SOL), extensor digitorum longus (EDL), lateral gastrocnemius (GL), plantaris (PL), tibialis antierior (TA), and medial gastrocnemius (GM) muscles of F344BN rats. *Significantly different compared with 12-month old rats, p <.05

Shown in Figure 2C, the relative cross-sectional area of type IIb fibers to total fiber area decreased by 12% in EDL, 26% in PL, 5% in TA, and 18% in GM (p <.05) between 12- and 35-month-old F344BN rats. There were no significant differences in SOL and GL (Figure 2C).

Skeletal Muscle Capillarity
When comparing the hind-limb muscles from 12- and 35-month-old F344BN rats, the transverse sections of DPP IV-stained and AP-stained muscles showed a significant increase in capillary density (p <.05) by 47% in SOL (Figure 3), 64% in PL (Figure 4), 84% in EDL, 48% in GL, 55% in TA, and 57% in GM (Figure 5A), along with concomitant decreases in fiber cross-sectional area, in each respective muscle (Figure 1B, p <.05).

View larger version (81K): [in this window] [in a new window]   Figure 3. Transverse section of soleus (SOL) muscle stained for dipeptidylpeptidase (DPP IV) and alkaline phosphatase (AP) showing venular (red) and arteriolar (blue) capillaries in 12-month-old (A) and 35-month-old (B) F344BN rats. Image depicts representative increases in venular capillary density in 35- compared to 12-month-old rats. Also seen is the decrease in average muscle fiber area found with increasing age shown in Figure 1B

View larger version (76K): [in this window] [in a new window]   Figure 4. Transverse section of plantaris (PL) muscle stained for dipeptidylpeptidase (DPP IV) and alkaline phosphatase (AP) showing venular (red) and arteriolar (blue) capillaries in 12-month-old (A) and 35-month-old (B) F344BN rats. Image depicts representative increases in venular capillary density in 35- compared to 12-month-old rats. Also seen is the decrease in average muscle fiber area found with increasing age shown in Figure 1B

View larger version (17K): [in this window] [in a new window]   Figure 5. A, Capillary densities varied from 47% in soleus (SOL) (smallest increase) to 84% in extensor digitorum longus (EDL) (largest increase) in the 35-month-old rats. B, Arteriolar capillary-to-fiber (C:F) ratio remained unchanged in SOL, EDL, lateral and medial gastrocnemius (GL, GM), and plantaris (PL), but increased 16% in tibialis anterior (TA) in 12- compared to 35-month-old F344BN rats. C, Venular C:F ratio increased 124% in PL, 70% in TA, and 70% in GM, and remained unchanged in SOL, EDL, and GL. *Significant differences between 12- and 35-month-old rats, p <.05

	DISCUSSION

Top Abstract Methods Results Discussion References

 
The principal finding of this study is that the ratio of venular capillaries to fibers was significantly greater in 35-month-old compared to 12-month-old male rats and in those muscles that also exhibited a significantly greater proportion of oxidative fiber types (type I or IIa) in 35-month-old compared to 12-month-old rats.

Muscle Fiber Capillarity and Fiber-Type Composition
There is evidence that arteriolar and venular segments of capillaries may be regulated independently, resulting in distinctive capillary patterning. To our knowledge, these are the first data to report differences in arteriolar and venular capillarity in young, middle-aged, and senescent rats (12-, 24-, and 35-month-old F344BN rats, respectively). In this study, we observed an increase in capillary density (Figure 5A) along with a decrease in muscle fiber cross-sectional area (Figure 1B) in the hind-limb muscles of 35-month-old compared to 12-month-old rats. Consistent with the majority of studies reporting the effect of age on muscle capillarity (28–33), we found that arteriolar C:F was unchanged between the three age groups we examined, with the exception of the TA muscle where the C:F was increased in 35-month-old compared to 12-month-old rats (Figure 5B). In contrast to the stability of arteriolar C:F, we found that venular C:F was significantly increased in three of the six hind-limb muscles (PL, TA, and GM) at 35 versus 12 months of age (Figure 5C). In these same muscles, we also observed an age-associated increase in the proportion of type I fibers (Figure 2A) and type IIa fibers (Figure 2B), except for the PL in which only type I fiber proportion increased significantly. In the same muscles (i.e., PL, TA, and GM), as well as in the EDL (Figure 2C), a decrease in proportion of type IIB fibers was also seen. These data support a shift away from glycolytic type IIb fibers toward the more oxidative type IIa and type I fibers. Because the PL, TA, and GM are muscles primarily composed of fast-twitch, type II, glycolytic fibers, it may be tempting to suggest that age has minimal or no impact on (either arteriolar or venular) capillaries in muscles that are predominantly slow-twitch (type I) oxidative fibers (i.e., SOL; Figure 2C), as evidenced by the greater venular C:F in PL, TA, and GM, but not in SOL (Figure 5C) in the 35-month-old compared 12-month-old rats. However, it should be noted that venular C:F was also not greater in either GL or EDL, both of which are composed of >60% type IIb fibers. But, despite the lack of statistical significance, there was in fact a similar tendency for increased venular C:F in the SOL and EDL (Figure 5C). It is also interesting to note that Suzuki and colleagues (38) also have reported greater venular capillarity in the SOL of sedentary Wistar rats at 13.5 months compared to 0.75 months (3 weeks), but because the age comparison is very different this may not be comparable. However, Suzuki and colleagues (39) have also reported increases in venular, but not arteriolar, capillary density in young female Wistar rats following 1 week of exercise training (treadmill running 5 days/week). But, after 4 and 5 weeks of training, venular capillary density was found to be decreased whereas arteriolar capillarity was increased (38,39). Because our study did not involve exercise training, it is impossible to know whether we might have seen a different proportional change in muscle capillarity had our rats also undergone exercise training.

Nevertheless, one might speculate that, because arterioles supply oxygenated blood, that exercise capacity would be maintained with age. However, we have previously shown reduced maximal oxygen consumption (VO_2max) in 35-month-old compared to 12-month-old F344BN rats (47). These data would indicate that reduced VO_2max in the oldest rats is not likely due to impaired peripheral gas exchange, as the number of arteriolar capillaries remained unchanged. Indeed, there is ample evidence pointing to the importance of muscle capillarity in the convective delivery of O₂ to exercising muscles (48–50). Because venular capillaries are thought to essentially comprise the trailing edge of gas exchange boundaries in peripheral organ tissues, it is likely that very little, if any, benefit to peripheral gas exchange would be seen from increasing venular capillaries. Thus the functional significance of increased venular capillaries, especially in the context of exercise, remains uncertain. Moreover, whether a similar pattern of increasing venular capillaries with age is found in humans still remains to be determined; however, given the differences in the phenotype of venular compared to arteriolar capillaries, such as greater leakiness and responsiveness to humoral factors, it is not surprising that exercise capacity and skeletal muscle function would decline with advancing age.

Muscle Atrophy (Sarcopenia)
Age-associated reductions in muscle mass have been reported in both humans (6) and rodents (31,51). In this study, as in previous studies (19,52), there was very little muscle mass loss from 12 to 24 months of age, whereas a significant loss in all muscles examined was apparent when comparing 24-month-old and 35-month-old animals (Figure 1A). This decline demonstrates that muscle fibers were significantly atrophied in the oldest rats. Although there are numerous reports on muscle atrophy in senescent rats, the absolute values of muscle mass have been quite variable, which in part may be due to the difference in life span of different strains studied. As previously noted, we chose to use F344BN rats because of their lower incidence of major pathologies with advanced age compared to other strains (41), but also because we would be able to compare these data against previous studies in our laboratory that separately assessed maximal oxygen consumption during exercise (47) and capillary-fiber interface per fiber mitochondrial volume (52) in similar age groups of F344BN rats. Indeed, the decreases in muscle mass in this study are similar to that which we have previously reported in these separate studies (47,52), as well as to several other studies using similarly aged F344BN rats (53–55). From these data, it is evident that the biggest change in mass occurred in muscles that contained predominantly fast-twitch (type II) fibers (Figures 1 and 2), and supports previous findings showing that decreases in muscle mass are related primarily to the atrophy of fast-twitch glycolytic muscle fibers (30,51,56). Moreover, because the average cross-sectional area of slow-twitch (type I) oxidative fibers is smaller than that of fast-twitch (type II) glycolytic fibers, the greater relative proportion of type II fiber compared to type I fibers (without any loss of total fiber number) likely contributed greatly to the decreased muscle mass in old versus young rats (51).

Methodological Considerations
We distinguished between arteriolar and venular segments of capillaries using a double staining method developed by Lodja (42), based on the fact that arteriolar endothelial cells selectively express AP enzyme. In contrast, venules lack AP but contain DPP IV. Validation of this double-staining method has been performed by Koyama and colleagues (57) by infusing 10-µm-diameter microspheres into the coronary artery and associating the localization of microsphere to the stained capillaries. Those data revealed that microspheres were found only in AP-stained capillaries, thus demonstrating the selectivity for AP staining for the arteriolar end of capillaries and inferring DPP IV selectivity to the venular capillaries.

Because the phenotype of endothelial cells is known to vary within the microvasculature (35), it is possible that one explanation for the conflicting outcomes reported in the literature regarding age-associated changes in capillarity may be due to the specificity of staining or immunolabeling to one versus the other end of the capillary. As with all staining techniques, the efficacy or completeness of the staining must also be considered. Even in our study, although AP and DPP IV are considered to be robust general stains for arteriolar and venular capillaries, variation in staining can still occur within some sections of muscle (45). Thus, in addition to biological variability in C:F between the respective muscles of the hind limb, not to mention potential differences due to animal strains, different methodologies for capillary identification may serve to confound comparisons between studies using different muscles, animal strains, and/or staining techniques. Interestingly, however, the age-related differences in arteriolar and venular capillarity we report here may help, at least in part, to explain the conflicting outcomes (i.e., increased, decreased, and/or no change) currently published in the literature with respect to age and muscle capillarity.

Summary
An age-related alteration in skeletal muscle morphology is shown in terms of muscle fiber type proportion and capillary vascularization. Consistent with many studies, we see a decrease in muscle fiber area and a concomitant increase in capillary density, yet no change in arteriolar C:F ratio, in old compared to young rats. However, we find that venular C:F ratio is increased in muscles undergoing a significant age-related shift from glycolytic to more oxidative fibers. Thus, there appears to be a greater venular capillary proportion in rat skeletal muscles, which have an increased percentage of cross-sectional area of oxidative fibers. These data support the notion of differential regulation of arteriolar and venular segments of capillaries and indicate that arteriolar and venular capillaries are affected differently with age. Based on the different methodologies used to assess and count capillaries, this finding may account for some of the discrepancies in the literature that report conflicting outcomes in age-associated alteration of skeletal muscle capillarity. Moreover, given the variation in the observed changes in capillarity and fiber-type composition between the six hind-limb muscles we studied, it is evident that the use of different specific muscles may also contribute to the disparities in the literature.

	Acknowledgments

Top Abstract Methods Results Discussion References

 
This work was supported by National Institutes of Health grant PO1 HL-1773 and TRDRP #14KT-0091. I. M. Olfert received funding support as a Parker B. Francis Fellow.

	Footnotes

Top Abstract Methods Results Discussion References

 
Decision Editor: Huber R. Warner, PhD

Received December 19, 2007

Accepted May 11, 2008

	References

Top Abstract Methods Results Discussion References

 

1. Gollnick PD, Armstrong RB, Saubert CW, Piehl K, Saltin B. Enzyme activity and fiber composition in skeletal muscle of untrained and trained men. J Appl Physiol. 1972;33:312-319.[Free Full Text]
2. Larsson L, Karlsson J. Isometric and dynamic endurance as a function of age and skeletal muscle characteristics. Acta Physiol Scand. 1978;104:129-136.[Medline]
3. Grimby G, Saltin B. The ageing muscle. Clin Physiol. 1983;3:209-218.[Medline]
4. Sato T, Akatsuka H, Kito K, Tokoro Y, Tauchi H, Kato K. Age changes in size and number of muscle fibers in human minor pectoral muscle. Mech Ageing Dev. 1984;28:99-109.[Medline]
5. Lexell J, Downham D, Sjostrom M. Distribution of different fibre types in human skeletal muscles. Fibre type arrangement in m. vastus lateralis from three groups of healthy men between 15 and 83 years. J Neurol Sci. 1986;72:211-222.[Medline]
6. Lexell J, Henriksson-Larsén K, Winblad B, Sjöström M. Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections. Muscle Nerve. 1983;6:588-595.[Medline]
7. Aniansson A, Hedberg M, Henning GB, Grimby G. Muscle morphology, enzymatic activity, and muscle strength in elderly men: a follow-up study. Muscle Nerve. 1986;9:585-591.[Medline]
8. Coggan AR, Spina RJ, King DS, et al. Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontol Biol Sci. 1992;47:B71-B76.
9. Grimby G, Danneskiold-Samsoe B, Hvid K, Saltin B. Morphology and enzymatic capacity in arm and leg muscles in 78-81 year old men and women. Acta Physiol Scand. 1982;115:125-134.[Medline]
10. Aniansson A, Grimby G, Hedberg M. Compensatory muscle fiber hypertrophy in elderly men. J Appl Physiol. 1992;73:812-816.[Abstract/Free Full Text]
11. Fayet G, Rouche A, Hogrel JY, Tome FM, Fardeau M. Age-related morphological changes of the deltoid muscle from 50 to 79 years of age. Acta Neuropathol. 2001;101:358-366.[Medline]
12. Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol. 1979;46:451-456.[Abstract/Free Full Text]
13. Larsson L, Sjödin B, Karlsson J. Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22–65 years. Acta Physiol Scand. 1978;103:31-39.[Medline]
14. Lexell J, Taylor CC, Sjostrom M. What is the cause of ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year old men. J Neurol Sci. 1988;84:275-294.[Medline]
15. Lexell J, Taylor CC. Variability in muscle fibre areas in whole human quadriceps muscle: effects of increasing age. J Anat. 1991;174:239-249.[Medline]
16. Ansved T, Edstrom L. Effects of age on fibre structure, ultrastructure and expression of desmin and spectrin in fast- and slow-twitch rat muscles. J Anat. 1991;174:61-79.[Medline]
17. Jakobsson F, Borg K, Edström L. Fibre-type composition, structure and cytoskeletal protein location of fibres in anterior tibial muscle. Comparison between young adults and physically active aged humans. Acta Neuropathol. 1990;80:459-468.[Medline]
18. Larsson L, Edström L. Effects of age on enzyme-histochemical fibre spectra and contractile properties of fast- and slow-twitch skeletal muscles in the rat. J Neurol Sci. 1986;76:69-89.[Medline]
19. Brown M, Hasser EM. Complexity of age-related change in skeletal muscle. J Gerontol Biol Sci. 1996;51A:B117-B123.[Abstract]
20. Lexell J, Taylor CC, Sjöström M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci. 1988;84:275-294.[Medline]
21. Aniansson A, Grimby G, Hedberg M, Krotkiewski M. Muscle morphology, enzyme activity and muscle strength in elderly men and women. Clin Physiol. 1981;1:73-86.
22. Davidson YS, Clague JE, Horan MA, Pendleton N. The effect of aging on skeletal muscle capillarization in a murine model. J Gerontol Biol Sci. 1999;54A:B448-B451.[Abstract]
23. Coggan AR, Spina RJ, Rogers MA, et al. Histochemical and enzymatic characteristics of skeletal muscle in master athletes. J Appl Physiol. 1990;68:1896-1901.[Abstract/Free Full Text]
24. Degens H, Turek Z, Hoofd LJC, Binkhorst RA. Capillary proliferation related to fibre types in hypertrophied aging rat m. plantaris. Adv Exp Med Biol. 1994;345:669-676.[Medline]
25. Degens H, Turek Z, Hoofd L, van't Hof MA, Binkhorst RA. Capillarisation and fibre types in hypertrophied m. plantaris in rats of various ages. Respir Physiol. 1993;94:217-226.[Medline]
26. Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol. 2000;88:1321-1326.[Abstract/Free Full Text]
27. Parizkova J, Eiselt E, Sprynarova S, Wachtlova M. Body composition, aerobic capacity, and density of muscle capillaries in young and old men. J Appl Physiol. 1971;31:323-325.[Free Full Text]
28. Kano Y, Shimegi S, Furukawa H, Matsudo H, Mizuta T. Effects of aging on capillary number and luminal size in rat soleus and plantaris muscles. J Gerontol Biol Sci. 2002;57A:B422-B427.[Abstract/Free Full Text]
29. Chilibeck PD, Paterson DH, Cunningham DA, Taylor AW, Noble EG. Muscle capillarization, O₂ diffusion distance, and VO₂ kinetics in old and young individuals. J Appl Physiol. 1997;82:63-69.[Abstract/Free Full Text]
30. Brown M. Change in fibre size, not number, in ageing skeletal muscle. Age Ageing. 1987;16:244-248.[Abstract/Free Full Text]
31. Brown M, Ross TP, Holloszy JO. Effects of ageing and exercise on soleus and extensor digitorum longus muscles of female rats. Mech Ageing Dev. 1992;63:69-77.[Medline]
32. Mitchell ML, Byrnes WC, Mazzeo RS. A comparison of skeletal muscle morphology with training between young and old Fischer 344 rats. Mech Ageing Dev. 1991;58:21-35.[Medline]
33. Proctor DN, Sinning WE, Walro JM, Sieck GC, Lemon PWR. Oxidative capacity of human muscle fiber types: effects of age and training status. J Appl Physiol. 1995;78:2033-2038.[Abstract/Free Full Text]
34. Rossiter HB, Howlett RA, Holcombe HH, Entin PL, Wagner HE, Wagner PD. Age is no barrier to muscle structural, biochemical and angiogenic adaptations to training up to 24 months in female rats. J Physiol (Lond). 2005;565:993-1005.[Abstract/Free Full Text]
35. Thurston G, Baluk P, McDonald DM. Determinants of endothelial cell phenotype in venules. Microcirculation. 2000;7:67-80.[Medline]
36. Phillips GD, Whitehead RA, Knighton DR. Initiation and pattern of angiogenesis in wound healing in the rat. Am J Anat. 1991;192:257-262.[Medline]
37. Stalmans I, Ng YS, Rohan R, et al. Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest. 2002;109:327-336.[Medline]
38. Suzuki J, Gao M, Batra S, Koyama T. Effects of treadmill training on the arteriolar and venular portions of capillary in soleus muscle of young and middle-aged rats. Acta Physiol Scand. 1997;159:113-121.[Medline]
39. Suzuki J, Kobayashi T, Uruma T, Koyama T. Time-course changes in arteriolar and venular portions of capillary in young treadmill-trained rats. Acta Physiol Scand. 2001;171:77-86.[Medline]
40. Myrhage R, Hudlicka O. Capillary growth in chronically stimulated adult skeletal muscle as studied by intravital microscopy and histological methods in rabbits and rats. Microvasc Res. 1978;16:73-90.[Medline]
41. Lipman RD, Chrisp CE, Hazzard DWG, Bronson RT. Pathologic characterization of Brown Norway, Brown Norway x Fischer 344, and Fischer 344 x Brown Norway rats with relation to age. J Gerontol Biol Sci. 1996;51A:B54-B59.[Abstract]
42. Lojda Z. Studies on dipeptidyl(amino)peptidase IV (glycyl-proline naphthylamidase). II. Blood vessels. Histochemistry. 1979;59:153-166.[Medline]
43. Mrazkova O, Grim M, Carlson BM. Enzymatic heterogeneity of the capillary bed of rat skeletal muscles. Am J Anat. 1986;177:141-148.[Medline]
44. Ogilvie RW, Feeback DL. A metachromatic DYE-ATP_ASE method for the simultaneous identification of skeletal muscle fiber types I, IIA, IIB and IIC. Stain Technol. 1990;65:231-241.[Medline]
45. Brooke MH, Kaiser KK. Muscle fiber types: How many and what kind? Arch Neurol. 1970;23:369-379.[Abstract/Free Full Text]
46. Padykula HA, Herman E. Factors affecting the activity of adenosine triphosphatase and other phosphatases as measured by histochemical techniques. J Histochem Cytochem. 1955;3:161-169.[Abstract]
47. Olfert IM, Balouch J, Mathieu-Costello O. Oxygen consumption during maximal exercise in Fischer 344 x Brown Norway F1 hybrid rats. J Gerontol A Biol Sci Med Sci. 2004;59:801-808.[Medline]
48. Henderson KK, Wagner H, Favret F, et al. Determinants of maximal O(2) uptake in rats selectively bred for endurance running capacity. J Appl Physiol. 2002;93:1265-1274.[Abstract/Free Full Text]
49. Howlett RA, Gonzalez NC, Wagner HE, et al. Genetic models in applied physiology: skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance. J Appl Physiol. 2003;94:1682-1688.[Abstract/Free Full Text]
50. Richardson R, Leek B, Gavin T, et al. Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO2 with small muscle mass exercise. Am J Respir Crit Care Med. 2004;169:89-96.[Abstract/Free Full Text]
51. Caccia MR, Harris JB, Johnson MA. Morphology and physiology of skeletal muscle in aging rodents. Muscle Nerve. 1979;2:202-212.[Medline]
52. Mathieu-Costello O, Ju Y, Trejo-Morales M, Cui L. Greater capillary-fiber interface per fiber mitochondrial volume in skeletal muscles of old rats. J Appl Physiol. 2005;99:281-289.[Abstract/Free Full Text]
53. Baker DJ, Hepple RT. Elevated caspase and AIF gene expression correlate with progression of sarcopenia during aging in male F344BN rats. Exp Gerontol. 2006;41:1149-1156.[Medline]
54. Fitts RH, Troup JP, Witzmann FA, Holloszy JO. The effect of ageing and exercise on skeletal muscle function. Mech Ageing Dev. 1984;27:161-172.[Medline]
55. Kovanen V, Suominen H. Effects of age and life-time physical training on fibre composition of slow and fast skeletal muscle in rats. Pflügers Arch. 1987;408:543-551.[Medline]
56. Tauchi H, Yoshioka T, Kobayashi H. Age change of skeletal muscles of rats. Gerontologia. 1971;17:219-227.[Medline]
57. Koyama T, Gao M, Uede T, et al. Different enzyme activities in coronary capillary endothelial cells. In: Oxygen Transport to Tissue XVIII. New York: Plenum Press; 1997:359–364.

This Article Abstract Full Text (PDF) Services Download to citation manager PubMed PubMed Citation