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Biomedical Sciences, College of Veterinary Medicine; Physiology, College of Medicine; and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We evaluated whether prior training would improve collateral blood flow (BF) to the calf muscles after acute-onset occlusion of the femoral artery. Exercise training was performed in the absence of any vascular occlusion. Adult male Sprague-Dawley rats (~325 g) were kept sedentary (n = 14), limited to cage activity, or exercise trained (n = 14) for 6 wk by treadmill running. Early in the day of measurement, animals were surgically prepared for BF determination, and the femoral arteries were occluded bilaterally. Four to five hours later, collateral BF was determined twice during treadmill running with the use of 141Ce and 85Sr microspheres: first, at a demanding speed and, second, after a brief rest and at a higher speed. The absence of any further increase in BF at the higher speed indicated that maximal collateral BF was measured. Prior training increased calf muscle BF by ~70% compared with sedentary animals; however, absolute BF remained below values previously observed in animals with a well-developed collateral vascular tree. Thus prior training appeared to optimize the use of the existing collateral circuit. This implies that altered vasoresponsiveness induced in normal nonoccluded vessels with exercise training serves to improve collateral BF to the periphery.
vascular adaptations; peripheral arterial insufficiency; microspheres; acute-onset vascular occlusion
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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IT IS WELL DOCUMENTED THAT submaximal endurance-type exercise training induces adaptations in the cardiovascular system (17). These adaptations extend throughout the circulatory system and involve conduit arteries, "feed" arteries, arterioles, and the capillary network. Structural and functional adaptations in the conduit supply arteries are important in establishing flow capacity and contribute to the regulation of blood flow to active muscles during exercise. Segal et al. (27) have reported that training increases the medial wall thickness of the abdominal aorta and femoral, axillary, and other primary arteries after extended exercise training. This structural modification may play a role in decreasing tangential wall stress of arteries when systolic blood pressure is elevated during exercise. Recent studies have showed that exercise training can alter vasomotor reactivity of resistance vessels (14, 30). Relatively short-duration daily exercise performed for a relatively brief duration of a few days to a few weeks increased endothelium-dependent vasodilation induced by acetylcholine (30). If the duration of exercise training is extended (e.g., 10-12 wk), enhanced endothelium-dependent vasodilation can be also found in the smaller 2A and 3A levels of arterioles (M. D. Delp and M. H. Laughlin, unpublished observations). These alterations in vasomotor activity induced by training are probably due to alterations in endothelial-mediated signals involving nitric oxide (NO) (14, 17, 30). Thus there is ample evidence to indicate that adaptations in systemic conduit arteries and smaller feed arteries and arterioles are induced by exercise training. These adaptations presumably impart a more effective vascular control while serving the metabolic demands of the working muscle during exercise.
Exercise training also induces peripheral adaptations that increase the aerobic capacity of muscle via increased number and volume of mitochondria (11), and enriched capillary density (12) of the active muscle. These physiological adaptations should decrease the diffusion distance between capillaries and mitochondria, prolong red blood cell transit time, and increase the surface area for nutrient exchange between the microcirculation and myocyte. Although these adaptations significantly improve aerobic capacity of the muscle and improve muscle performance (38, 39), they have little to do with flow capacity to muscle, as this is the function of the upstream resistance and conduit vessels.
After acute occlusion of a primary supply artery, the affected distal tissue will be completely dependent on the collateral circulation for nutrient supply. Collateral vessels exist in many vascular circuits, including the upper thigh of animals (31-33, 35). After occlusion of the femoral artery, sufficient collateral blood flow proceeds through these vessels to meet the resting metabolic needs of the distal limb muscle, the tissue most at risk of ischemia (13, 35). It is apparent from X-ray images of the arterial tree of the thigh that flow through these preexisting collateral vessels arises from large conduits originating from the internal iliac artery (hypogastric trunk) and its branches (31, 35), vessels that normally serve the muscle of the thigh. These vessels and/or their connections that anastomose to the distal tissue are responsive to NO modulation via nitro-L-arginine methyl ester (L-NAME) (32, 33). Whether this circumventing circuit can be preconditioned to better serve their collateral function in the face of an acute vascular accident is presently unknown. Thus we posed the following question: do the vascular adaptations induced by exercise training impart an advantage to increase peripheral collateral blood flow immediately after experimental occlusion of the femoral artery? Results that follow demonstrate that prior exercise training modifies the response of existing vessels within the thigh to increase collateral-dependent blood flow to the calf muscles when the femoral artery is occluded.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Experimental design. Adult male Sprague-Dawley rats were divided into two groups: sedentary animals (n = 14), which were limited to cage activity, and trained animals (n = 14), which were exercised by treadmill running. After 6 wk of training, rats were randomly taken from each group for blood flow measurement with the radiolabeled microsphere technique (see Blood flow determination) in vivo during treadmill exercise. Two treadmill speeds were used to ensure measurement of maximal collateral-dependent blood flow.
Animal care. Rats (~325 g), obtained from Taconic Farms (Germantown, NY), were housed in a temperature-controlled room (20 ± 1°C) with a 12:12-h light-dark cycle and were given Purina Lab Chow and tap water ad libitum. On arrival, all animals were briefly familiarized to the treadmill protocol by running 5-10 min/day for 4-5 days. This brief exposure to treadmill running ensures good running performance for blood flow determination. Furthermore, previous evidence from this laboratory has shown that this procedure does not confound the experiment for animals kept sedentary (37, 43).
Exercise training. A progressively intense treadmill training program was used. Rats began running at 30 m/min at a 15% grade on a rodent treadmill (Quinton); exercise duration increased from ~20 to 60 min/day over the first 2 wk, where it remained for the 6-wk duration of the study. Rats ran 5 days/wk. When the rats were able to run for 60 min/day, 1-min sprints at 40-60 m/min were introduced beginning at the 60th min. As the rats were able, additional sprints were included at 10-min intervals.
Surgical procedures. On the morning of the experiment day, all animals were subjected to bilateral ligation of the femoral arteries at a site 5-6 mm distal to the inguinal ligament, ~4-5 h before blood flow measurement. This procedure effectively creates acute-onset peripheral arterial insufficiency in rats (37, 43). Flow reserve to the hindlimb is significantly reduced; however, flow capacity to the collateral-dependent distal hindlimb remains sufficient to exceed flow demands for quiescent resting muscle. Thus this procedure does not produce signs of ischemia at rest and/or tissue necrosis.
The details of the ligation procedure have been described previously (43). In brief, the animals were anesthetized with ketamine (100 mg/kg)-acepromazine (0.5 mg/kg), and their femoral arteries were isolated just distal to the inguinal ligament. A ligature was placed tightly around each femoral artery. This produces a uniform ligation, and the animals recovered within 30-40 min with 100% success.Blood flow determination. Surgical preparation for blood flow determination has been described in detail previously (43). Immediately after bilateral femoral artery ligation, a catheter (PE 50 tubing) was placed in the arch of the aorta via the left carotid artery for infusion of radiolabeled microspheres. A second catheter was placed in the caudal artery for monitoring blood pressure and heart rate as well as for obtaining the reference blood sample during microsphere infusion. Both catheters were filled with heparinized saline (100 IU/ml) and led under the skin to the back of neck. Animals were run on a treadmill for blood flow determination later in the day (~4-5 h postsurgery, as done previously; see Refs. 37 and 43).
Muscle blood flow was determined with the use of radiolabeled microspheres (85Sr and 141Ce, 15 ± 0.1-µm diameter; NEN, Boston, MA) during the second minute of treadmill running, as done routinely (37, 43). Blood flows measured at this time are dependent on the running speed. A well-mixed suspension solution of microspheres was carefully infused though the carotid catheter, followed by a saline flush, over ~20 s. At the same time, a reference blood sample was withdrawn from the caudal artery at a rate of 500 µl/min (starting 10 s before microsphere infusion). Assessment of maximal collateral-dependent blood flows was sought by determining flows at a low but demanding (20 m/min at 15% grade) and a relatively high treadmill speed (25 m/min at 15% grade for sedentary group, 30 m/min at 15% grade for trained group). Femoral artery occlusion removes ~90% of the flow reserve to the calf muscles. Thus the calf muscles are relatively ischemic during exercise, even at the low treadmill speed. Similar blood flows at the two speeds indicate that peak vascular conductance has been reached. After exercise, the rats were killed with an overdose of pentobarbital sodium (injection); tissue samples comprising each entire hindlimb and the middle third of each kidney were then sampled. All tissue samples, together with the reference blood flow sample, were counted to a 1% error (Beckman Autogamma 8000) and corrected for "spillover" between isotope counting windows. Muscle blood flow (in ml · min
1 · 100 g1) was
calculated as
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Biochemical analysis.
Muscle sections from superficial white (predominantly fast-twitch
white) and deep red (predominantly fast-twitch red) sections of the
quadriceps were dissected immediately after the animal was killed. All
muscle samples were frozen and stored at 
80°C until analysis for
citrate synthase activity, as described by Srere (29).
Statistical analysis. Statistical analysis included analysis of variance for main treatment effects of prior training, with repeated measures for replicate determinations within animals of each group (e.g., for blood flow, heart rate, blood pressure, and muscle citrate synthase activity). Individual mean differences were compared using Tukey's procedure (30). Significant differences were recognized at P < 0.05. Values are expressed as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Tissue masses.
There were no significant differences in body weights and hindlimb
tissue masses between the sedentary and trained groups (cf. Table
1).
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Training response.
As shown in Fig. 1, at the start of
exercise, rats ran ~25 min/day and were able to run 60 min/day after 2 wk of training. This exercise protocol did not markedly
reduce the body weights of trained animals (cf. Table 1). The activity
of a mitochondrial enzyme marker, citrate synthase, increased
(P < 0.01) significantly in both white (15 ± 1.4 vs. 10 ± 1.4 µmol · min1 · g1) and red
(76 ± 2.8 vs. 60 ± 3.9 µmol · min1 · g1)
sections of quadriceps muscles in the trained and sedentary animals,
respectively.
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Blood pressure and heart rate. As shown in Table 1, blood pressures of trained animals were not different from those of the sedentary group at preexercise and during exercise. Heart rates of trained rats tended to be lower than those of the sedentary animals, but there were no statistical differences between the two groups (P > 0.05).
Muscle blood flow.
Blood flows could not be determined from three animals (one in the
sedentary group and two in the trained group) because of complications
in surgery and/or an inability to obtain the reference withdrawal
sample through the caudal catheter. Furthermore, the second blood flow
determination could not be determined in three animals; these are noted
(see Tables 2-4).
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1 · 100 g1,
respectively; n = 47) during each flow determination.
Similarly, there was an excellent match in blood flow distribution
across hindlimbs within each animal (0.99 ± 0.02 left
hindlimb/right hindlimb blood flow; n = 47). Thus
labeled microspheres appeared to be well mixed into cardiac output and
provide a valid assessment of flow distribution within the animals
during exercise.
Even though the exercising blood pressures were similar between
sedentary and trained groups (cf. Table 1), blood flows to the entire
hindlimb, as well as the component proximal and distal limb segments,
were significantly higher in the trained group at both speeds
(P < 0.01). This includes collateral-dependent blood
flows to the distal hindlimb tissues (e.g., calf muscles) of trained
animals, which were ~70% higher than those in the sedentary group
(P < 0.01).
As shown in Table 2, blood flows measured
at a higher speed (25 or 30 m/min depending on group) in both
treatment groups were similar to the flows measured at the lower speed
(20 m/min) in the same treatment group; this observation provides
evidence that peak blood flows were achieved in the
collateral-dependent muscles. Significant training effects on hindlimb
blood flows are illustrated in Fig. 2,
where blood flow values at low and high speeds were combined. Also
included in Fig. 2 are reference blood flows for normal animals running
at 20 m/min in the absence of vascular occlusion that were obtained in
previous work from our laboratory (36).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Exercise training induces vascular adaptation.
The results of this study indicate that 6 wk of exercise training in
normal rats induces vascular adaptations that improve muscle blood flow
during exercise in acute-onset peripheral arterial insufficiency. Blood
flows were greater throughout the hindlimbs of the trained compared
with the sedentary rats. Most significant to the interest of this study
is the observation that blood flow to the distal hindlimb muscles was
greater (~70%, P < 0.05) in trained rats. For
example, sections of the calf muscles of trained rats had blood flows
that were 10-30 ml · min1 · 100 g1 greater than in the same muscles of sedentary rats.
This is the region of muscle most at risk of ischemia after occlusion
of the femoral artery (13, 35). It can be seen in Fig. 2
that proximal occlusion of the femoral artery reduces blood flow
capacity of the calf muscle by >90%, far more than in the muscles of
the thigh. It is well known that exercise training can increase
skeletal muscle blood flow capacity (17) by structural
expansion of the arterial tree. In normal animals, training-induced
vascular remodeling has been generally viewed as changes in the normal
vascular tree, not the collateral circulation. However, it appears that
this view derives primarily from studies demonstrating a lack of an effect of exercise training on the coronary collateral circulation in
normal animals. Our results demonstrate that the vasculature of the
hindlimb muscles differs from the coronary vascular bed in that
exercise training in normal nonoccluded animals improves the ability of
hindlimb vasculature to deliver blood flow in the face of acute-onset
vascular occlusion. Thus prior exercise conditioning could help protect
tissue at risk of ischemia after a peripheral vascular accident.
Change of vascular resistance by exercise training. Systemic blood pressures were not significantly different between sedentary and trained groups, so the increased blood flow in trained animals must result from decreased vascular resistance. Because the arterioles and arteriolar network possess most of the vascular resistance in skeletal muscle and because exercise training can increase blood flow capacity of normal skeletal muscle (17), it may be expected that adaptations in the normal resistance vasculature within, for example, the calf muscles contributed to the increased blood flow observed in this study. However, there are two reasons that make it unlikely that training-induced decreases in calf muscle resistance (Rcalf) contributed significantly to the increased blood flow during exercise after acute femoral ligation. First, after acute femoral artery occlusion, vascular resistance in the distal limb tissue is minimized by muscle contractions (i.e., Rcalf is so minimal during ischemic contractions that further decreases would have little effect on blood flow). Second, after femoral artery ligation, the pressure perfusing the calf muscles is decreased by 80-85% (15, 33). This would calculate to a pressure of ~25 mmHg in the sedentary animals of this study. Therefore, decreases in Rcalf will have small effects on blood flow. Although training-induced changes in microvascular anatomy (angiogenesis) and control of vascular resistance are present, they cannot fully explain the increase in blood flows observed in the present study. Accordingly, after bilateral ligation of the femoral arteries, blood flow to the calf muscles should be dependent on the resistance of the upstream collateral circuit, which circumvents the proximal obstruction (35). As a result, we interpret the increased blood flow to the calf muscles of the trained animals as an increase in flow capacity of the upstream collateral circuit. The following represents an expanded view of the vascular issues that we believe are involved.
Figure 3 presents a schematic illustrating the location of vascular resistance for the hindlimb muscles of the normal rat (Fig. 3A) and after acute femoral ligation (Fig. 3B). In normal rats, total vascular resistance from iliac artery to capillary in the distal calf muscle is the sum of resistance of the femoral artery (Rfem) and the feed arteries and arteriolar resistance in the muscle microcirculation (Rcalf). The thigh muscles are perfused primarily by branches arising from the internal iliac artery (hypogastric trunk, see Ref. 10) and, in part, by branches from the distal femoral artery (Yang and Terjung, unpublished observations). As illustrated in Fig. 3, total vascular resistance to thigh muscles is the sum of resistance of the internal iliac and branching arteries (Ri-iliac), conduit vessels arising from the distal femoral artery (Rd-ham), and feed arteries and arterioles in the muscle microcirculation (Rthigh). As shown, in normal rats, Rcalf and Rthigh are much greater than Rfem, Ri-iliac, and Rd-ham; thus muscle blood flow during exercise is primarily determined by the resistance vessels of the active muscle. In contrast, after femoral occlusion, there is no flow through the femoral artery, so Rfem is not involved in perfusion of the distal limb muscle. Rather, total vascular resistance to the calf muscles in the distal limb is now the sum of Rcalf and Ri-iliac + Rd-ham. Importantly, it should be recognized that the circumventing circuit includes the resistance of the internal iliac and its branch arteries in the thigh (Ri-iliac) plus the resistance of the vessels that anastomose in the distal hamstrings (Rd-ham). This resistance is relatively high and accounts for the large pressure drop across the thigh in the presence of femoral artery occlusion (15, 33). Interestingly, flow through the circumventing circuit could involve retrograde flow through the vessels that normally arise from the distal femoral artery (Rd-ham). Furthermore, true microvascular "collateral" vessels, as traditionally viewed, may be included in the circumventing circuit; however, their involvement would likely exert extensive resistance that would reduce their importance, supplying blood flow well downstream to the distant calf muscles after acute vascular occlusion. Because Rcalf is minimal during exercise in the presence of bilateral femoral ligation (35, 41), the primary vascular resistance defining flow to the calf muscles is the sum of Rd-ham and Ri-iliac.
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Structural vascular adaptation.
It has been well recognized that exercise training induces structural
remodeling to enlarge the collateral circuit in the periphery
(40-42), just as in the coronary circuit (cf. Ref.
18), when exercise is performed in the presence of vascular
obstruction. The present results, however, indicate that skeletal
muscle collateral circuit flow capacity is increased by exercise
training even in the absence of arterial insufficiency. It seems
possible that an increased caliber of the circumventing circuit
vessels, including the internal iliac artery and its branches,
contributes to the increased collateral flow capacity. This would
simply require a structural enlargement of the vessels that compose
Ri-iliac and Rd-ham in
the normal course of training, a response not supported by previous
work (5, 15, 27). On the other hand, it is possible that
improved vasoresponsiveness of the involved conduits is the primary
factor. In support of this latter possibility, it is important to note
that the collateral-dependent flow capacity of the trained animals in
this study is well within the flow capacity of sedentary animals that
have been inactive after occlusion of the femoral arteries (37,
42) for a time to realize the full caliber of the collateral
vessels (3). Thus the present results are not the high
flows (~70-80 ml · min1 · 100 g1) characteristic of structural enlargement of the
collateral tree (37, 42). Furthermore, the absolute
collateral flow increase with pretraining is similar to that
established by acute angiotensin-converting enzyme inhibition
on collateral blood flow, results that implicate modulation of vascular
tone (36). Although we cannot rule out possible structural
changes, we favor an interpretation that the training effect is due to
an improved vasoresponsiveness of the vessels composing the
circumventing circuit.
Altered control of collateral vascular resistance. It is reasonable to propose that training alters control of the internal iliac artery, its branches, and other conduit arteries that contribute to collateral circuit vascular resistance. A number of studies have demonstrated that exercise hyperemia and vasomotor reactivity of skeletal muscle arteries are altered by exercise training (2, 15, 16, 22). This likely involves altered function of the endothelium (5, 14, 17, 19, 28, 30) and vascular smooth muscle (15-17) of conduit arteries supplying skeletal muscle. Such an improved vasomotor responsiveness of the internal iliac and its branches could impart a smaller pressure drop across these conduit arteries of the thigh; this would lead to a greater pressure perfusing the collateral-dependent calf muscles. In addition, this would contribute to the greater blood flow observed in the thigh muscle during exercise in the trained animals. Thus our results are consistent with an improved function of the internal iliac arterial tree contributing to the improved flow capacity of the collateral circuit.
The signal(s) for adaptation.
Exercise generates a number of potential signals for adaptive changes
in gene expression in arteries. It has been proposed that increases in
muscle blood flow, associated with each bout of exercise, generate a
"shear stress" signal for vascular adaptation to exercise training
(20, 21, 23, 28). Wall shear stress (Sw) is
increased by an increase in blood flow (Q) as described in the
following equation: Sw = 4Q
/
ri3 (where is viscosity and
ri is internal radius of the artery). Thus, when
flow increases, Sw at the vessel wall increases. Acutely, flow-induced dilatation of the artery increases radius and thereby returns Sw toward normal levels. It appears that substances
that signal remodeling and altered phenotype of endothelial and smooth muscle cells are also released in response to increased Sw
(1, 4, 6, 8).
Significance of this study. Collectively, this evidence supports our hypothesis that an improved vasoresponsiveness, possibly mediated by eNOS activity, contributes to the improved collateral blood flow of trained animals after acute-onset peripheral vascular occlusion. We believe that this occurred through adaptations in the internal iliac and its branches, as they form part of the circumventing circuit after femoral artery occlusion. Therefore, we believe our results are most consistent with the hypothesis that exercise training in normal animals signals functional adaptations in preexisting arteries that function as part of the circumventing circuit after acute-onset peripheral arterial insufficiency. These adaptations allow improved collateral blood flow capacity in the periphery, where existing anastomosing vessels are available to circumvent the vascular obstruction.
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ACKNOWLEDGEMENTS |
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We gratefully acknowledge J. King and K. Furukoshi for excellent technical assistance in this study.
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FOOTNOTES |
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This study was supported by National Heart, Lung, and Blood Institute Grants HL-37387 and HL-36088.
Address for reprint requests and other correspondence: R. L. Terjung, Biomedical Sciences, College of Veterinary Medicine, E102 Veterinary Medicine Bldg., Univ. of Missouri, Columbia, MO 65211 (E-mail: terjungr{at}missouri.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 11 February 2000; accepted in final form 9 May 2000.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Adair, TH,
Gay WJ,
and
Montani J.
Growth regulation of the vascular system: evidence for a metabolic hypothesis.
Am J Physiol Regulatory Integrative Comp Physiol
259:
R393-R404,
1990
2.
Armstrong, RB,
and
Laughlin MH.
Exercise blood flow patterns within and among rat muscles after training.
Am J Physiol Heart Circ Physiol
246:
H59-H68,
1984
3.
Conrad, MC,
Anderson JL,
and
Garrett JB.
Chronic collateral growth after femoral artery occlusion in the dog.
J Appl Physiol
31:
550-555,
1971
4.
Davies, PF,
and
Tripathi SC.
Mechanical stress mechanisms and the cell: an endothelial paradigm.
Circ Res
72:
239-245,
1993
5.
Delp, MD,
and
Laughlin MH.
Time course of enhanced endothelium-mediated dilation in aorta of trained rats.
Med Sci Sports Exerc
29:
1454-1461,
1997[ISI][Medline].
6.
Dzau, VJ,
and
Gibbons GH.
The emerging concept of vascular remodeling.
N Engl J Med
330:
1431-1438,
1994
7.
Frangos, JA,
Eskin SG,
McIntire LV,
and
Ives CL.
Flow effects on prostacyclin production by cultured human endothelial cells.
Science
227:
1477-1479,
1985
8.
Furchgott, RF,
and
Vanhoutte PM.
Endothelium-derived relaxing and contracting factors.
FASEB J
3:
2007-2018,
1989[Abstract].
9.
Grabowski, EF,
Jaffer EA,
and
Weksler BB.
Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress.
J Lab Clin Med
105:
36-43,
1985[ISI][Medline].
10.
Greene, EC.
Anatomy of the Rat. New York: Hafner, 1963.
11.
Holloszy, JO.
Biochemical adaptations to exercise: aerobic metabolism.
Exerc Sport Sci Rev
1:
45-71,
1973[Medline].
12.
Hudlicka, O,
Brown M,
and
Egginton S.
Angiogenesis in skeletal and cardiac muscle.
Physiol Rev
72:
369-417,
1992
13.
Ito, WD,
Arras M,
Scholz D,
Winkler B,
Htun P,
and
Schaper W.
Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion.
Am J Physiol Heart Circ Physiol
273:
H1255-H1265,
1997
14.
Koller, A,
Huang A,
Sun D,
and
Kaley G.
Exercise training augments flow-dependent dilation of rat skeletal muscle arterioles: role of endothelial nitric oxide and prostaglandins.
Circ Res
76:
544-550,
1995
15.
Lash, J,
and
Bohlen HG.
Functional adaptations of rat skeletal muscle arterioles to aerobic exercise training.
J Appl Physiol
72:
2052-2062,
1992
16.
Lash, J,
and
Bohlen HG.
Time- and order-dependent changes in functional and NO-mediated dilation during exercise training.
J Appl Physiol
82:
460-468,
1997
17.
Laughlin, ML,
Korthuis RJ,
Duncker DJ,
and
Bache RJ.
Control of blood flow to cardiac and skeletal muscle during exercise.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am Physiol Soc, 1996, sect. 12, chapt. 16, p. 705-769.
18.
Laughlin, MH,
and
McAllister RM.
Exercise training-induced coronary vascular adaptation.
J Appl Physiol
73:
2209-2225,
1992
19.
McAllister, RM,
and
Laughlin MH.
Short-term exercise training alters responses of porcine femoral and brachial arteries.
J Appl Physiol
82:
1438-1444,
1997
20.
Miller, VM,
Aarhus LL,
and
Vanhoutte PM.
Modulation of endothelium-dependent responses by chronic alterations of blood flow.
Am J Physiol Heart Circ Physiol
251:
H520-H527,
1986
21.
Miller, VM,
and
Vanhoutte PM.
Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow.
Am J Physiol Heart Circ Physiol
255:
H446-H451,
1988
22.
Musch, TI,
Haidet GC,
Ordway GA,
Longhurst JC,
and
Mitchell JH.
Training effects on regional blood flow response to maximal exercise in fox hounds.
J Appl Physiol
62:
1724-1732,
1987
23.
Nadaud, S,
Philippe M,
Arnal J,
Michel J,
and
Soubrier F.
Sustained increase in aortic endothelial nitric oxide synthase expression in vivo in a model of chronic high blood flow.
Circ Res
79:
857-863,
1996
24.
Nishida, K,
Harrison DG,
Navas JP,
Fisher AA,
Dockery SP,
Uematsu M,
Nerem RM,
Alexander RW,
and
Murphy TJ.
Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.
J Clin Invest
90:
2092-2096,
1992.
25.
Noris, M,
Morigi M,
Donadelli R,
Aiello S,
Foppolo M,
Todeschini M,
Orisio S,
Remuzzi G,
and
Remuzzi A.
Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions.
Circ Res
76:
536-543,
1995
26.
Ranjan, V,
Xiao Z,
and
Diamond SL.
Constitutive NOS expression in cultured endothelial cells is elevated by fluid shear stress.
Am J Physiol Heart Circ Physiol
269:
H550-H555,
1995
27.
Segal, SS,
Kurjiaka DT,
and
Caston AL.
Endurance training increases arterial wall thickness in rats.
J Appl Physiol
74:
722-726,
1993
28.
Sessa, WC,
Pritchard K,
Seyedi N,
Wang J,
and
Hintze TH.
Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
Circ Res
74:
349-353,
1994
29.
Srere, PA.
Citrate synthase.
Methods Enzymol
5:
432-434,
1962.
30.
Sun, D,
Huang A,
Koller A,
and
Kaley G.
Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats.
J Appl Physiol
76:
2241-2247,
1994
31.
Takeshita, S,
Zheng LP,
Brogi E,
Kearney M,
Pu LQ,
Bunting S,
Ferrara N,
Symes JF,
and
Isner JM.
Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.
J Clin Invest
93:
662-670,
1994.
32.
Unthank, JL,
Nixon JC,
and
Dalsing MC.
Acute compensation to abrupt occlusion of rat femoral artery prevented by NO synthase inhibitors.
Am J Physiol Heart Circ Physiol
268:
H2523-H2530,
1995.
33.
Unthank, JL,
Nixon JC,
and
Dalsing MC.
Nitric oxide maintains dilation of immature and mature collaterals in rat hindlimb.
J Vasc Res
33:
471-479,
1996[ISI][Medline].
34.
Woodman, CR,
Muller JM,
Laughlin MH,
and
Price EM.
Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs.
Am J Physiol Heart Circ Physiol
273:
H2575-H2579,
1997.
35.
Yang, HT,
Deschenes MR,
Ogilvie RW,
and
Terjung RL.
Basic fibroblast growth factor increases collateral blood flow in rats with femoral arterial ligation.
Circ Res
76:
62-69,
1996.
36.
Yang, HT,
Dinn RF,
and
Terjung RL.
Training increases muscle blood flow in rats with peripheral arterial insufficiency.
J Appl Physiol
69:
1353-1359,
1990
37.
Yang, HT,
Feng Y,
Allen LA,
Protter A,
and
Terjung RL.
Efficacy and specificity of bFGF increased collateral flow in experimental peripheral arterial insufficiency.
Am J Physiol Heart Circ Physiol
278:
H1966-H1973,
2000
38.
Yang, HT,
Ogilvie RW,
and
Terjung RL.
Low-intensity training produces muscle adaptations in rats with femoral artery stenosis.
J Appl Physiol
71:
1822-1829,
1991
39.
Yang, HT,
Ogilvie RW,
and
Terjung RL.
Peripheral adaptations in trained aged rats with femoral artery stenosis.
Circ Res
74:
235-243,
1994
40.
Yang, HT,
Ogilvie RW,
and
Terjung RL.
Training increases collateral-dependent muscle blood flow in aged rats.
Am J Physiol Heart Circ Physiol
268:
H1174-H1180,
1995
41.
Yang, HT,
Ogilvie RW,
and
Terjung RL.
Heparin increases exercise-induced collateral blood flow in rats with femoral artery ligation.
Circ Res
76:
448-456,
1995
42.
Yang, HT,
Ogilvie RW,
and
Terjung RL.
Exercise training enhances basic fibroblast growth factor-induced collateral blood flow.
Am J Physiol Heart Circ Physiol
274:
H2053-H2061,
1998
43.
Yang, HT,
and
Terjung RL.
Angiotensin-converting enzyme inhibition increases collateral-dependent muscle blood flow.
J Appl Physiol
75:
452-457,
1993
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P < 0.001.
P, change in pressure;
Qt, total blood flow; Qthigh, thigh blood flow;
Qcalf, calf blood flow.