| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR |
1 Division of Exercise Physiology, Department of Physiology and Pharmacology, and the Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA
2 Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0673, USA
3 Department of Integrative Physiology, University of Colorado, Boulder, CO 80309-0354, USA
4 Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
1.6 times more active during dark periods and 4 times more active during light periods than old rats. In addition, young rats had approximately one additional feed artery perforating both the soleus (young, 3.3 ± 0.2; old, 2.6 ± 0.2 vessels; P < 0.05) and gastrocnemius (young, 8.8 ± 0.1; old, 7.5 ± 0.2 vessels, P < 0.05) muscles compared with old rats. However, average vessel wall shear stress at rest was similar between young and old rats (soleus: Y, 65 ± 5; O, 64 ± 5 dynes cm–2; gastrocnemius: Y, 329 ± 22; O, 327 ± 27 dynes cm–2) resulting from a larger vessel diameter in arteries from old rats. In conclusion, lower activity levels of old rats likely contribute to resistance artery rarefaction and, consequently, this provides a plausible mechanism for the altered blood flow patterns observed during exercise in aged skeletal muscle.
(Received 25 February 2006;
accepted after revision 22 April 2006;
first published online 27 April 2006)
Corresponding author M. D. Delp: Division of Exercise Physiology, Department of Physiology and Pharmacology, and the Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA. Email: mdelp{at}hsc.wvu.edu
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Shear stress, the frictional force acting at the interface of the vessel wall and flowing blood, is a crucial modulator of vessel luminal diameter. Specifically, with alterations in shear stress, vessels respond by altering lumen diameter transiently through the release of vasoactive agents such as nitric oxide and prostacyclin (Frangos et al. 1985; Olesen et al. 1988; Yoshizumi et al. 1989; Cooke et al. 1991) and, if the change in shear persists, by restructuring vessel morphology (Kamiya & Togawa, 1980; Langille & O'Donnell, 1986; Langille et al. 1989; Delp et al. 2000). Whether changes in vascular morphology and shear stress occur with ageing remain unknown. The purpose of this investigation was to test the hypothesis that arterial rarefaction occurs in the soleus and gastrocnemius muscles of old rats, but that increases in vessel diameter previously reported to occur with old age (Muller-Delp et al. 2002a; Spier et al. 2004) serve to maintain wall shear stress relative to that in young animals. Because age-related differences in physical activity and corresponding muscle hyperaemia may provide the stimulus for the putative arterial rarefaction in muscles of old rats, a secondary purpose of this investigation was to determine whether spontaneous physical activity differs between young and old rats. Findings from this investigation will thus provide a mechanistic link between ageing, physical activity and vascular remodelling, and show whether structural vascular changes contribute to altered blood flow distribution and exercise intolerance in senescent individuals.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Activity monitoring
A telemetry system (VitalView 4000, Mini-Miter, Bend, OR, USA) was used to monitor heart rate (HR), core body temperature and activity in conscious, freely moving animals. Rats were anaesthetized (isoflurane 2.5% in 100% O2) and a small sterile transmitter (volume, 1.13 ml; Standard E-Mitter, Mini-Mitter, Bend) was implanted in the abdomen under aseptic conditions. Buprenorphine hydrochloride (0.05 mg kg–1
S.C.) was administered as an analgesic after surgery. Animals were allowed a recovery period of 1 week before activity measurements were made. During the recovery period, rats were monitored daily by a veterinarian for signs of infection and discomfort.
For measures of physical activity (basic index of cage movement), HR and body temperature, animals were housed individually in custom-made cages (54 cm x 29 cm x 15 cm) placed upon TR-4000 receivers (Mini-Mitter Co., Bend). These cages were located in a room separate from animals involved in other studies to minimize possible influences which could affect telemetry measurements (e.g. noise). Only personnel involved in this investigation entered the room to monitor and supply food and water. These cages, which are considerably larger than standard rat cages, were designed to allow the maximum area for free movement. HR, core body temperature and activity were measured at 30-s intervals for 2 weeks, with mean HR, temperature and activity values assessed during active (dark cycle) and inactive (light cycle) periods of the day (12 h light–12 h dark). The Mini-Mitter transmitter records activity counts that are generated when the transmitter changes position and/or orientation relative to the TR-4000 receiver antenna. Position change can be in any plane (i.e. horizontal or vertical) to cause counts to be recorded. Each time there is a change in position or orientation of the transmitter relative to the receiver, an automatic gain circuit (AGC) is activated. Each time the AGC is activated, an activity count is generated. Counts are totalled during the sample epoch selected (i.e. 30-s period), and then reported as a whole number of activity counts for that epoch. The activity count, as well as data collected on HR and body temperature, is stored until the end of the 30-s period and then data are collected anew for the following period. These stored periods were then averaged for the light and dark daily cycles for the 2-week measurement session. Following successful measurements of daily activity levels, rats were anaesthetized with sodium pentobarbital (60 mg kg–1 I.P.) and killed by decapitation before measuring vascular morphology (see below).
Vascular geometry and morphology
Once the animal had been killed, the soleus–plantaris–gastrocnemius muscle group was carefully dissected free and placed in a filtered calcium-free physiological saline solution (PSS) buffer at 4°C containing in (mM): NaCl 147, KCl 4.7, NaH2PO2 1.2, MgSO4 1.17, glucose 5.0, pyruvate 2.0 and Mops 3.0; pH 7.4. The feed arteries perforating the soleus muscle and all portions of the gastrocnemius muscle (i.e. red, mixed and white portions) were identified and isolated with the use of a stereomicroscope, removed from the muscle and transferred to a Lucite tissue viewing chamber. Subsequently, both ends of the resistance vessel were cannulated with glass micropipettes filled with the filtered PSS and secured to the pipettes with 11-O ophthalmic suture as previously described (McCurdy et al. 2000; Muller-Delp et al. 2002a,b). After cannulation, each vessel in the tissue chamber was transferred to the stage of an inverted microscope (Olympus IX70) coupled to a video camera (Panasonic BP310) and video caliper (Microcirculation Research Institute, Texas A&M University). Intraluminal pressure in the isolated resistance vessels was set at 60 cmH2O, and 10–4 M sodium nitroprusside (SNP) was added to the vessel chamber to prevent development of spontaneous tone and ensure maximal dilatation. Leaks were detected by pressurizing the vessel and then closing the valves to the reservoirs and verifying that intraluminal pressure remained constant. Vessels that were free of leaks were equilibrated for at least 1 h at 37°C before their maximal diameter and wall thickness were measured; the bathing solution was replaced every 20 min during this period.
Bulk blood flow measurements
To prevent possible radioactive contamination of instruments used for vascular morphology measurements, a separate group of rats was utilized for quantifying resting blood flow to the soleus and gastrocnemius muscles. Blood flow was determined in a separate cohort of 14 Fisher-344 rats (n
= 7 per group) using the radionuclide-tagged microsphere technique (Laughlin et al. 1982) in the conscious standing condition. Initially, rats were anaesthetized with isoflurane (2.5% in 100% O2). Polyethlene catheters (PE-10 connected to PE-50) were implanted in the right carotid and caudal (tail) arteries. The carotid artery catheter was advanced 2–3 mm rostral to the aortic valve and secured. The tail artery catheter was advanced towards the bifurcation of the descending aorta and secured. After the incisions were closed (4-O silk), anaesthesia was terminated and the animal was given 
2 h to recover as Flaim et al. (1984) demonstrated that cardiac or circulatory dynamics, regional blood flow, arterial blood gases and acid–base status are stable in the awake unrestrained rat 1–6 h after gas anaesthesia. The tail artery catheter was connected to a 5-ml glass syringe, which was attached to a Harvard withdrawal pump (model 907, Cambridge, MA, USA). The carotid artery catheter was connected to a pressure transducer (BP100, ADInstruments) to monitor mean arterial pressure.
Radiolabelled (46Sc or 85Sr) microspheres (15 µm diameter; DuPont/NEN, Boston, MA, USA) were used for blood flow measurements as previously described (Laughlin et al. 1982; Delp et al. 1991). Prior to infusion, the microspheres were agitated by sonication to suspend the beads and prevent clumping. At 30 s prior to initiating infusion, blood withdrawal from the caudal artery at 0.25 ml min–1 was begun. The right carotid artery catheter was disconnected from the pressure transducer and a specified microsphere (250000 microspheres) was infused into the ascending aorta, which was then flushed with warmed saline to ensure clearance of the beads. Blood withdrawal from the caudal artery continued for 45 s after microsphere infusion.
Following the microsphere infusion, the rats were killed with an overdose of sodium pentobarbital (>80 mg kg–1) via the right carotid artery catheter. After verifying correct placement of the carotid catheter, the left and right soleus muscle, gastrocnemius muscle and kidneys were removed. The gastrocnemius muscle was then sectioned into red (RG), mixed (MG) and white (WG) portions of the muscle, which correspond to the predominately high oxidative type I and IIA fibres (RG), a mixed fast fibre-type population (MG) and the predominately low oxidative type IIB fibres (WG) (Delp & Duan, 1996). The radioactivity level of the tissues was determined by a three-channel gamma scintillation counter (Packard Auto Gamma Spectrometer, model 5230) set to record the peak energy activity of each isotope for 5 min. Total blood flow to each tissue was calculated by the reference sample method (Ishise et al. 1980; Musch & Terrell, 1992) and expressed in ml min–1 (100 g tissue)–1. Adequate mixing of the microspheres was verified by demonstrating a <15% difference in blood flow to the right and left kidneys.
Estimated shear stress
Shear stress determination.
The maximum internal luminal radius (i.e. rmax) of the feed arteries was calculated from the measured inner perimeters of the media via a video caliper (Microcirculation Research Institute). Luminal cross sectional area (CSA) was calculated as:
|
|
) was then calculated using the equation:
|
|
is the apparent blood viscosity (0.035 Poise) (Liposky, 1995) and Q is the blood flow rate through the vessel. Q in the conscious standing condition was derived using the following equation:
|
|
65% of rmax. Statistical analysis
Unpaired student's t tests were used to determine the significance of differences in the morphological parameters of resistance arteries, body mass, soleus and gastrocnemius muscle mass, and the soleus and gastrocnemius muscle to body mass ratios between young and old groups. A one-way ANOVA was used to compare wall shear stress, feed artery number and muscle blood flow between young and old animals. The Student–Newman–Keuls method was used as a post hoc test to determine the significance of differences among means. All values are presented as means ± S.E.M. P < 0.05 was required for significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The body mass of old rats was significantly greater than that of young animals (Table 1). There was a significant atrophy observed in the gastrocnemius muscle with ageing (P < 0.05), and a tendency for atrophy in the soleus muscle (P = 0.06; Table 1).
|
Soleus muscle. As illustrated in Fig. 1, on average there was approximately one less feed artery perforating the soleus muscle of old (2.6 ± 0.2 vessels muscle–1) versus young (3.4 ± 0.2 vessels muscle–1; P < 0.05) animals. The average luminal diameter (young, 158 ± 5 µm; old, 177 ± 5 µm; P < 0.05) and luminal CSA (Fig. 2) of the individual feed arteries perforating the soleus muscle were significantly greater in the old versus young group. Average wall thickness (young, 23.5 ± 2.3 µm; old, 23.2 ± 2.2 µm) was not different between the young and old soleus muscle arteries, nor was the wall to lumen ratio (Fig. 3).
|
|
|
Blood flow and mean arterial pressure
There were no age-related differences in mean arterial pressure (young, 112 ± 7 mmHg; old, 117 ± 6 mmHg) or in blood flow to soleus or gastrocnemius muscles or gastrocnemius parts (Fig. 4A). For both age groups, conscious resting blood flow was greater in the soleus than in the gastrocnemius muscle. In addition, resting blood flow was greatest in the red portion, followed by the mixed and white portions of the gastrocnemius muscle (Fig. 4A).
|
As illustrated in Fig. 4B, there were no age-related differences in calculated feed artery shear stress in the soleus or gastrocnemius muscles during standing, although shear stress was greater in the gastrocnemius than in the soleus muscle for both age groups. Within the gastrocnemius muscle, estimated shear stress was less in the old than in the young arteries from the red and white gastrocnemius, but was not significantly different in the mixed portion of gastrocnemius muscle (Fig. 4B).
Physical activity
Young animals demonstrated greater spontaneous activity levels (i.e. gross index of cage movement) during daily light and dark periods than old animals (Fig. 5A). However, the greatest difference in activity was observed during the light period where young animals were 4 times more active than the old group (versus
1.6 times more active during the dark period). Both young and old animals demonstrated an elevated HR (Fig. 5B) and body temperature (Fig. 5C) during the more active nocturnal period.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
) mismatching in aged skeletal muscle (Behnke et al. 2005). A secondary purpose of this investigation was to determine whether old rats exhibited reduced levels of spontaneous activity in order to ascertain whether different activity patterns are associated with vascular alterations induced by old age. The results demonstrate that during both the light and dark periods of the day, old rats are more sedentary than young rats (Fig. 5). As skeletal muscle perfusion increases during nocturnal periods of the day in young rats (Delp et al. 1991), the reduced levels of activity and muscle metabolism in old rats would attenuate skeletal muscle perfusion, and over time could act to alter the morphology of feed arteries perforating these muscles. It is worth noting that the study design utilized herein does not allow the effects of ageing and reduced spontaneous activity to be investigated separately. Therefore, further studies investigating whether enhancing physical activity (e.g. exercise training) can reduce the age-related differences in vascular structure observed in this study are warranted.
Ageing and vascular remodelling
Previous work has shown that the luminal diameter of single isolated arterioles from the gastrocnemius muscle of old rats is larger than that of young animals (Muller-Delp et al. 2002a). Based on established patterns of arterial remodelling (Kamiya & Togawa, 1980; Langille, 1993), such a change in vascular structure suggests that these vessels from old rats are exposed to a chronically higher blood flow to the muscle. However, several studies (as well as the present study) have shown that muscle blood flow is not greater at rest in old animals (Delp et al. 1998; Musch et al. 2004). This apparent paradox between vascular structure and direct measures of muscle perfusion could result from ageing-induced changes in the vascular network, which analysis of vessel diameter from the muscle would not address. Data from the present study demonstrate that in addition to enlarged luminal diameters, there are also fewer feed arteries supplying blood to the muscle (Fig. 1). Therefore, even though resting muscle blood flow does not differ between young and old rats (Fig. 4A), the blood flow rate through the remaining feed arteries to the muscle must be greater with ageing, which is supported by greater red blood cell velocities in capillaries from old skeletal muscle (Russell et al. 2003). Such an increase in blood flow would elevate the intravascular shear stress in the remaining arteries and provide a stimulus for a structural increase in maximal diameter over time. Notwithstanding structural changes in individual feed arteries, the decrease of the vascular network at the level of the feed arteries in skeletal muscle of old rats would severely perturb the ability of the vasculature to modulate blood flow to active motor units within exercising muscle, which appears to be the case (Musch et al. 2004).
Given that resting muscle blood flow does not differ between young and old rats, the nature of the stimulus that induces the rarefaction of the arterial network associated with old age in muscle is still unknown. Several possible mechanisms may exist including: (1) a reduction in vascular endothelial growth factor (VEGF) protein and mRNA expression in skeletal muscle (Croley et al. 2005) and VEGF promoter activity in smooth muscle cells (Rivard et al. 1999); (2) an increased vascular oxidative stress (Van Der Loo et al. 2000; Francia et al. 2004; Sullivan et al. 2004) contributing to endothelial cell apoptosis (Asai et al. 2000); and (3) a chronically reduced muscular perfusion and shear stress associated with diminished physical activity and muscle metabolism. With regard to this latter possibility, Pries et al. (1998; 2003),, postulated that, in addition to wall shear stress, the metabolic condition of the muscle is key to structural adaptation and the stability of microvascular networks. Specifically, if flow increases preferentially through one arterial segment, and correspondingly decreases through another, over time one would expect a shrinking and eventual recession of the low-flow arterial branch. However, a ‘metabolic response’ (i.e. the release of metabolites from downstream, poorly perfused tissue) would act to stabilize vascular segments and preserve low-flow pathways (Pries et al. 1998, 2001, 2003). Therefore, in old rats, the reduction in spontaneous locomotion and muscle activity may fail to provide a sufficiently robust local metabolic stimulus for vascular stability. This scenario, coupled with reduced pro-angiogenic agents in aged blood vessels (e.g. reduced bioavailability of nitric oxide) (Muller-Delp et al. 2002a; Woodman et al. 2002; Spier et al. 2004), could result in an obligatory increase in the luminal diameter of those arteries supporting higher flows, and the eventual recession and disappearance of the low-flow vessels.
Ageing, activity and blood flow
As evidenced from cage movement patterns (Fig. 5), the old rats were less active than the young animals during both the light and dark daily periods. We speculate that the reduced spontaneous activity in the old rats is key to understanding the altered vascular morphology observed in this study. Briefly, when an animal is standing at rest the soleus muscle, which is composed mainly of type I fibres, is recruited, resulting in a high resting blood flow (Laughlin & Armstrong, 1982; Delp & Duan, 1996). In addition, the predominant fibre type recruited with low-intensity exercise is that of the highly oxidative type IIA fibres (Armstrong et al. 1977, 1987; Laughlin & Armstrong, 1982; Delp & Duan, 1996), which is the primary fibre type within the red portion of the gastrocnemius muscle. With treadmill walking (15 m min–1), for example, the largest absolute increase in blood flow within the hindlimb musculature is to the red gastrocnemius (increase of 235%), with a smaller increase in the mixed portion of the muscle (138%), and no change in blood flow to the white portion (Laughlin & Armstrong, 1982). Moreover, only during high-intensity exercise does blood flow increase to the white muscle (Laughlin & Armstrong, 1982). Therefore, with less-spontaneous activity (as cage activity is within the low-intensity domain, based upon comparisons of heart rates measured here in and those reported as a function of exercise intensity (Laughlin & Armstrong, 1982)), the daily hyperaemic responses to the soleus and high-oxidative portions of the gastrocnemius muscle of old rats would be lower over the 24-h period. The consequent diminution in shear stress within the muscle feed arteries, which as detailed above, would be likely to lead to less metabolic stabilization and fewer arterial networks in high oxidative muscle. Furthermore, it is likely that reduced daily blood flow patterns also attenuate the overall cyclic stretch that the vessel would be subjected to during that period. Indeed, reduced exposure to cyclic stretch is one possible mechanism contributing to age-related increases in arterial stiffness (Cox, 1983).
It is interesting that, although old rats demonstrated lower levels of spontaneous physical activity compared with young rats, HR values were significantly elevated in the old animals. This probably reflects a cardiovascular deconditioning effect (McDonald et al. 1992; Mujika & Padilla, 2001; Hansen et al. 2004), which may include elevations in sympathetic nerve activity (Ebert et al. 1992) in the old animals, which would result in a higher HR for a given level of activity.
Functional ramifications of altered vascular structure
Ageing causes a profound redistribution of skeletal muscle blood flow during submaximal exercise (Musch et al. 2004). Specifically, blood flow decreases to highly oxidative muscles (e.g. soleus and red gastrocnemius) while increasing to low oxidative muscle (e.g. white gastrocnemius), which is a similar perfusion pattern to that in which inactivity is chronically imposed with hindlimb unloading (McDonald et al. 1992), and the inverse of that occurring with exercise training (Armstrong & Laughlin, 1984). Given the multifaceted effects of ageing on the functional and structural vascular properties, the delineation of precise mechanisms responsible for the reduction in vascular conductance associated with old age (Wahren et al. 1974; Koch et al. 2003; Lawrenson et al. 2003; Musch et al. 2004; Donato et al. 2006) is challenging. From the present study, as well as others (Muller-Delp et al. 2002b), it appears that ageing-induced alterations in vascular structure and function are fibre-type specific. Within the soleus muscle, the culmination of fewer feed arteries (Fig. 1) and an impairment of endothelium-dependent vasodilatation associated with old age (Muller-Delp et al. 2002a; Spier et al. 2004) would act to attenuate muscle blood flow during exercise (Musch et al. 2004). Within the gastrocnemius muscle, the largest reduction in perforating feed arteries occurred in the red portion of gastrocnemius muscle (>20% fewer vessels; Fig. 1). Functionally, it could be assumed that feed arteries from the red gastrocnemius muscle demonstrate similar endothelial dysfunction associated with old age as that observed in the soleus muscle (Muller-Delp et al. 2002a; Woodman et al. 2003), because arteries from both respond similarly to endothelium-dependent vasodilator agents (McAllister, 2003). Therefore, the same mechanisms as detailed for the soleus are likely to be responsible for the diminished blood flow in the red gastrocnemius of old rats during exercise, although specific functional studies of the effects of ageing on vascular reactivity within the red gastrocnemius have not been conducted.
The white gastrocnemius was the only muscle part that did not demonstrate an age-associated reduction in the number of feed arteries. The maintenance of feed artery number along with the enlargement of luminal diameter resulted in a 38% increase in feed artery luminal CSA within this low oxidative muscle of old rats (Fig. 2). Furthermore, arteries from the white gastrocnemius do not show any decrement in responsiveness to endothelium-dependent vasodilators such as acetylcholine with ageing (Muller-Delp et al. 2002a; Woodman et al. 2002). Therefore, unlike that occurring in high oxidative muscle, structural and functional vascular alterations associated with old age do not appear to limit blood flow and vascular conductance in low oxidative skeletal muscles. The combined effects of ageing on vascular structure and function in high and low oxidative muscles could therefore underlie the decrease in blood flow to high oxidative muscle and increased perfusion of low oxidative muscle during submaximal exercise, despite total hindlimb muscle blood flow being unchanged by old age (Musch et al. 2004). Changes in muscle perfusion patterns associated with old age therefore result in a mismatch of O2 delivery to muscle oxidative capacity. Such a conclusion is further supported by the observations that microvascular O2 pressure is lower in muscles from old animals at rest and during contractions, indicating an O2 delivery to 
mismatching (Behnke et al. 2005). This mismatch could alter the metabolic milieu (Wilson et al. 1977) and contribute to the increased end-exercise ADPfree concentrations demonstrated in the elderly (Taylor et al. 1997).
Significance and conclusions
In old rats there is a structural remodelling of the microcirculation (e.g. arterial rarefaction) in skeletal muscle (Fig. 1). The consequences of arterial rarefaction appear to include greater heterogeneities in Q to 
matching (Russell et al. 2003; Behnke et al. 2005), thus potentially limiting capillary O2 efflux (Honig & Odoroff, 1981), as well as restricting perfusion at a given workload (Donato et al. 2006). Moreover, the alterations in blood flow distribution associated with old age would supply an excess of O2 to less metabolically active regions of the muscle, with suboptimal O2 delivery to the more active muscles, which explains why aged muscle demonstrates a reduced O2 uptake at a matched convective O2 delivery (Hepple et al. 2003). These results are also consistent with the hypothesis that physical inactivity, and the corresponding reduction in muscle metabolism, is the stimulus for observed vascular rarefaction in the highly oxidative muscle and muscle parts. It is known that increased activity (e.g. exercise training) can reverse or reduce many of the detriments in vascular function related to old age (Spier et al. 2004; Donato et al. 2005). Although the angiogenic response to exercise training does not appear to be affected by age (Rossiter et al. 2005), it remains to be determined whether exercise training can result in arterial neogenesis in aged skeletal muscle.
In summary, skeletal muscle from old rats has fewer feed arteries perforating the muscle, with a compensatory arterial luminal enlargement which maintains resting shear stress. These structural alterations associated with old age are presumed to contribute to the altered vascular conductance during submaximal exercise, resulting in reduced O2 delivery to the active musculature. Thus, the suboptimal O2 delivery to active muscles that occurs during exercise in old age, because of altered vascular structure and function (Muller-Delp et al. 2002a; Spier et al. 2004; Donato et al. 2005), would result in an increased O2 deficit and forced reliance upon substrate level phosphorylation, ultimately causing exercise intolerance in the aged population.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Armstrong RB & Laughlin MH (1984). Exercise blood flow patterns within and among rat muscles after training. Am J Physiol 246, H59–H68.[Medline]
Armstrong
RB, Marum
P, Saubert
CWT, Seeherman
HJ
&
Taylor
CR (1977). Muscle fiber activity as a function of speed and gait. J Appl Physiol
43, 672–677.
Asai
K, Kudej
RK, Shen
YT, Yang
GP, Takagi
G, Kudej
AB
et al. (2000). Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol
20, 1493–1499.
Behnke BJ, Delp MD, Dougherty PJ, Musch TI & Poole DC (2005). Effects of aging on microvascular oxygen pressures in rat skeletal muscle. Respir Physiol Neurobiol 146, 259–268.[CrossRef][Medline]
Cooke JP, Rossitch E Jr, Andon NA, Loscalzo J & Dzau VJ (1991). Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest 88, 1663–1671.[Medline]
Cox RH (1983). Age-related changes in arterial wall mechanics and composition of NIA Fischer rats. Mech Ageing Dev 23, 21–36.[CrossRef][Medline]
Croley
AN, Zwetsloot
KA, Westerkamp
LM, Ryan
NA, Pendergast
AM, Hickner
RC, Pofahl
WE
&
Gavin
TP (2005). Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women. J Appl Physiol
99, 1872–1879.
Delp
MD, Colleran
PN, Wilkerson
MK, McCurdy
MR
&
Muller-Delp
J (2000). Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity. Am J Physiol Heart Circ Physiol
278, H1866–H1873.
Delp
MD
&
Duan
C (1996). Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle. J Appl Physiol
80, 261–270.
Delp
MD, Evans
MV
&
Duan
C (1998). Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats. J Appl Physiol
85, 1813–1822.
Delp MD, Manning RO, Bruckner JV & Armstrong RB (1991). Distribution of cardiac output during diurnal changes of activity in rats. Am J Physiol 261, H1487–H1493.[Medline]
Donato
AJ, Lesniewski
LA
&
Delp
MD (2005). The effects of aging and exercise training on endothelin-1 vasoconstrictor responses in rat skeletal muscle arterioles. Cardiovasc Res
66, 393–401.
Donato
AJ, Uberoi
A, Wray
DW, Nishiyama
S, Lawrenson
L
&
Richardson
RS (2006). Differential effects of aging on limb blood flow in humans. Am J Physiol Heart Circ Physiol
290, H272–H278.
Ebert TJ, Morgan BJ, Barney JA, Denahan T & Smith JJ (1992). Effects of aging on baroreflex regulation of sympathetic activity in humans. Am J Physiol 263, H798–H803.[Medline]
Flaim SF, Nellis SH, Toggart EJ, Drexler H, Kanda K & Newman ED (1984). Multiple simultaneous determinations of hemodynamics and flow distribution in conscious rat. J Pharmacol Methods 11, 1–39.[CrossRef][Medline]
Fleg
JL
&
Lakatta
EG (1988). Role of muscle loss in the age-associated reduction in VO2 max. J Appl Physiol
65, 1147–1151.
Francia
P, Delli Gatti
C, Bachschmid
M, Martin-Padura
I, Savoia
C, Migliaccio
E
et al. (2004). Deletion of p66shc gene protects against age-related endothelial dysfunction. Circulation
110, 2889–2895.
Frangos
JA, Eskin
SG, McIntire
LV
&
Ives
CL (1985). Flow effects on prostacyclin production by cultured human endothelial cells. Science
227, 1477–1479.
Hansen AL, Johnsen BH, Sollers JJ 3rd, Stenvik K & Thayer JF (2004). Heart rate variability and its relation to prefrontal cognitive function: the effects of training and detraining. Eur J Appl Physiol 93, 263–272.[CrossRef][Medline]
Hepple
RT, Hagen
JL, Krause
DJ
&
Jackson
CC (2003). Aerobic power declines with aging in rat skeletal muscles perfused at matched convective O2 delivery. J Appl Physiol
94, 744–751.
Honig CR & Odoroff CL (1981). Calculated dispersion of capillary transit times: significance for oxygen exchange. Am J Physiol 240, H199–H208.[Medline]
Inbar O, Oren A, Scheinowitz M, Rotstein A, Dlin R & Casaburi R (1994). Normal cardiopulmonary responses during incremental exercise in 20- to 70-yr-old men. Med Sci Sports Exerc 26, 538–546.
Irion GL, Vasthare US & Tuma RF (1987). Age-related change in skeletal muscle blood flow in the rat. J Gerontol 42, 660–665.[Medline]
Ishise S, Pegram BL, Yamamoto J, Kitamura Y & Frohlich ED (1980). Reference sample microsphere method: cardiac output and blood flows in conscious rat. Am J Physiol 239, H443–H449.[Medline]
Kamiya A & Togawa T (1980). Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am J Physiol 239, H14–H21.[Medline]
Koch
DW, Leuenberger
UA
&
Proctor
DN (2003). Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation. J Physiol
551, 337–344.
Langille BL (1993). Remodeling of developing and mature arteries: endothelium, smooth muscle, and matrix. J Cardiovasc Pharmacol 21 (suppl. 1), S11–S17.[Medline]
Langille BL, Bendeck MP & Keeley FW (1989). Adaptations of carotid arteries of young and mature rabbits to reduced carotid blood flow. Am J Physiol 256, H931–H939.[Medline]
Langille
BL
&
O'Donnell
F (1986). Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science
231, 405–407.
Laughlin MH & Armstrong RB (1982). Muscular blood flow distribution patterns as a function of running speed in rats. Am J Physiol 243, H296–H306.[Medline]
Laughlin
MH, Armstrong
RB, White
J
&
Rouk
K (1982). A method for using microspheres to measure muscle blood flow in exercising rats. J Appl Physiol
52, 1629–1635.
Lawrenson
L, Poole
JG, Kim
J, Brown
C, Patel
P
&
Richardson
RS (2003). Vascular and metabolic response to isolated small muscle mass exercise: effect of age. Am J Physiol Heart Circ Physiol
285, H1023–H1031.
Liposky H (1995). Shear stress in the circulation. In Flow-Dependent Regulation of Vascular Function ed. Bevan IA, Kaley G, Rubanyi GM, pp. 28–45. Oxford University Press, New York.
McAllister
RM (2003). Endothelium-dependent vasodilation in different rat hindlimb skeletal muscles. J Appl Physiol
94, 1777–1784.
McCurdy
MR, Colleran
PN, Muller-Delp
J
&
Delp
MD (2000). Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles. J Appl Physiol
89, 398–405.
McDonald
KS, Delp
MD
&
Fitts
RH (1992). Effect of hindlimb unweighting on tissue blood flow in the rat. J Appl Physiol
72, 2210–2218.
Mujika I & Padilla S (2001). Cardiorespiratory and metabolic characteristics of detraining in humans. Med Sci Sports Exerc 33, 413–421.
Muller-Delp
JM, Spier
SA, Ramsey
MW
&
Delp
MD (2002a). Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles. Am J Physiol Heart Circ Physiol
283, H1662–H1672.
Muller-Delp
JM, Spier
SA, Ramsey
MW, Lesniewski
LA, Papadopoulos
A, Humphrey
JD
&
Delp
MD (2002b). Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles. Am J Physiol Heart Circ Physiol
282, H1843–H1854.
Musch
TI, Eklund
KE, Hageman
KS
&
Poole
DC (2004). Altered regional blood flow responses to submaximal exercise in older rats. J Appl Physiol
96, 81–88.
Musch TI & Terrell JA (1992). Skeletal muscle blood flow abnormalities in rats with a chronic myocardial infarction: rest and exercise. Am J Physiol 262, H411–H419.[Medline]
Olesen SP, Clapham DE & Davies PF (1988). Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331, 168–170.[CrossRef][Medline]
Pries
AR, Reglin
B
&
Secomb
TW (2001). Structural adaptation of vascular networks: role of the pressure response. Hypertension
38, 1476–1479.
Pries
AR, Reglin
B
&
Secomb
TW (2003). Structural response of microcirculatory networks to changes in demand: information transfer by shear stress. Am J Physiol Heart Circ Physiol
284, H2204–H2212.
Pries AR, Secomb TW & Gaehtgens P (1998). Structural adaptation and stability of microvascular networks: theory and simulations. Am J Physiol 275, H349–H360.[Medline]
Proctor
DN, Shen
PH, Dietz
NM, Eickhoff
TJ, Lawler
LA, Ebersold
EJ, Loeffler
DL
&
Joyner
MJ (1998). Reduced leg blood flow during dynamic exercise in older endurance-trained men. J Appl Physiol
85, 68–75.
Rivard
A, Fabre
JE, Silver
M, Chen
D, Murohara
T, Kearney
M, Magner
M, Asahara
T
&
Isner
JM (1999). Age-dependent impairment of angiogenesis. Circulation
99, 111–120.
Rossiter
HB, Howlett
RA, Holcombe
HH, Entin
PL, Wagner
HE
&
Wagner
PD (2005). Age is no barrier to muscle structural, biochemical and angiogenic adaptations to training up to 24 months in female rats. J Physiol
565, 993–1005.
Russell
JA, Kindig
CA, Behnke
BJ, Poole
DC
&
Musch
TI (2003). Effects of aging on capillary geometry and hemodynamics in rat spinotrapezius muscle. Am J Physiol Heart Circ Physiol
285, H251–H258.
Spier
SA, Delp
MD, Meininger
CJ, Donato
AJ, Ramsey
MW
&
Muller-Delp
JM (2004). Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles. J Physiol
556, 947–958.
Sullivan
JC, Loomis
ED, Collins
M, Imig
JD, Inscho
EW
&
Pollock
JS (2004). Age-related alterations in NOS and oxidative stress in mesenteric arteries from male and female rats. J Appl Physiol
97, 1268–1274.
Taylor DJ, Kemp GJ, Thompson CH & Radda GK (1997). Ageing: effects on oxidative function of skeletal muscle in vivo. Mol Cell Biochem 174, 321–324.[CrossRef][Medline]
Van Der Loo
B, Labugger
R, Skepper
JN, Bachschmid
M, Kilo
J, Powell
JM
et al. (2000). Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med
192, 1731–1744.
Wahren J, Saltin B, Jorfeldt L & Pernow B (1974). Influence of age on the local circulatory adaptation to leg exercise. Scand J Clin Lab Invest 33, 79–86.[Medline]
Wilson DF, Erecinska M, Drown C & Silver IA (1977). Effect of oxygen tension on cellular energetics. Am J Physiol 233, C135–C140.[Medline]
Woodman
CR, Price
EM
&
Laughlin
MH (2002). Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol
93, 1685–1690.
Woodman
CR, Price
EM
&
Laughlin
MH (2003). Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries. J Appl Physiol
95, 2164–2170.
Yoshizumi M, Kurihara H, Sugiyama T, Takaku F, Yanagisawa M, Masaki T & Yazaki Y (1989). Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun 161, 859–864.[CrossRef][Medline]
|
Acknowledgements |
|---|
This article has been cited by other articles:
|
|
 |
|
  E. Jebelovszki, C. Kiraly, N. Erdei, A. Feher, E. T. Pasztor, I. Rutkai, T. Forster, I. Edes, A. Koller, and Z. Bagi High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2558 - H2564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Behnke, M. D. Delp, D. C. Poole, and T. I. Musch Aging potentiates the effect of congestive heart failure on muscle microvascular oxygenation J Appl Physiol, November 1, 2007; 103(5): 1757 - 1763. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
P < 0.05 versus light period; *P < 0.05 versus young. AU, arbitary units.