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Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65211
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
McAllister, Richard M., and M. Harold Laughlin.
Short-term exercise training alters responses of porcine femoral
and brachial arteries. J. Appl.
Physiol. 82(5): 1438-1444, 1997.
The primary
purpose of this study was to test the hypothesis that short-term
exercise training enhances endothelium-dependent relaxation of porcine
femoral and brachial arteries. Miniature swine ran on a treadmill for 1 h at 3.5 miles/h, twice daily, for 7 consecutive days (Trn;
n = 8). Compared with sedentary
controls (Sed; n = 7), Trn swine
exhibited increased skeletal muscle citrate synthase activity
(P < 0.05). Vascular rings ~3 mm
in axial length were prepared from segments of femoral and brachial
arteries, and responses to vasoactive agents were determined in vitro.
Sensitivity to bradykinin (BK) was enhanced in brachial vascular rings
from Trn swine compared with those from Sed swine, as indicated by
lower concentration of vasorelaxing agent eliciting 50% of maximal
response values [Sed, 8.63 ± 0.09 (
log M); Trn, 9.07 ± 0.13; P < 0.05]. This
difference between groups was preserved in brachial rings in which
formation of nitric oxide and vasodilator prostaglandins were inhibited
[Sed, 8.57 ± 0.17 (log M); Trn, 8.97 ± 0.13;
P < 0.05]. Sensitivity to BK
was not different between Sed and Trn in femoral arterial rings.
Relaxation responses to the calcium ionophore A-23187 and sodium
nitroprusside were not altered with training. Femoral and brachial
arterial rings from Trn swine, compared with those from Sed swine,
exhibited augmented vasocontraction across a range of concentrations
and increased sensitivity to norepinephrine (all
P < 0.05). These findings indicate
that responses of porcine femoral and brachial arteries change in
response to short-term training. Together with findings from previous
studies involving longer term training, our data suggest that vascular adaptations may differ at different time points during long-term endurance exercise training.
norepinephrine; bradykinin; endothelium
INTRODUCTION ADAPTATIONS IN VASCULAR CONTROL mechanisms could
contribute to the greater skeletal muscle blood flow response to
high-intensity exercise observed after a period of endurance exercise
training (14, 15). Enhanced responses to
endothelium-dependent vasodilating stimuli (4, 9, 24) have been
reported for arterial vessels from endurance-trained rats. Studies
conducted in larger animals and humans, however, have yielded equivocal
results. We recently reported that exercise training did not induce
adaptations in the endothelium of conduit arteries serving skeletal
muscle in miniature swine (11). We had hypothesized that daily exposure to increased blood flow, over a 16- to 20-wk period of training, would induce adaptations in the vascular endothelium that could enhance
dilation during acute exercise. Furthermore, Green and colleagues (6)
reported no improvement in human forearm blood flow responses to
several doses of the endothelium-dependent vasodilator methacholine
after 4 wk of forearm muscle training. In the coronary vascular bed,
however, it has been reported that just 1 wk of exercise training is
associated with enhanced dilation of the circumflex coronary artery,
another conduit vessel exposed to increased blood flow during training
bouts (26). Enhanced endothelium-dependent dilation in the canine
coronary arteries studied by Wang et al. (26) was subsequently found to
be associated with increased nitric oxide synthase activity in the
coronary vascular endothelium (20). This adaptation would offer the
potential for greater release of the endothelium-derived vasodilator
nitric oxide. In contrast, our studies in swine (18) and those of
others in dogs (19) have found that endothelium-dependent relaxation of
coronary arteries is not enhanced after long-term (i.e., 10-20 wk)
exercise training.
In attempting to reconcile these differing findings, we have speculated
that endothelium-dependent vasodilation is enhanced early (i.e., after
just a few days) in a period of exercise training in large animals
(10). This adaptation could serve to buffer increased shear stress, a
consequence of increased blood flow, experienced by the vascular wall
during initial training bouts. Subsequently, structural adaptations
(e.g., increased vessel diameter) may occur that minimize or even
eliminate the need for enhanced endothelium-dependent vasodilation.
Available data from studies of the coronary vascular bed are consistent
with this contention; however, data for skeletal muscle vasculature are
scarce. Nonetheless, similar stimuli for vascular adaptation, such as
increased blood flow, would be expected to be present in the coronary
and skeletal muscle vascular beds during training bouts. Findings for
long-term exercise training effects on responses of conduit vessels
serving skeletal muscle are similar to those from the coronary
circulation in that endothelium-dependent vasodilation is unchanged
after long-term training (11). Effects of short-term training on
skeletal muscle vasculature are unknown.
Thus the primary purpose of this study was to test the hypothesis that
short-term endurance exercise training enhances endothelium-dependent relaxation of arteries serving skeletal muscle. A secondary purpose of
the study was to determine whether short-term training would enhance
endothelium-independent vasorelaxation and blunt vasocontraction. Such
adaptations could also contribute to an improved muscle blood flow
response to acute exercise. In the present study, we examined responses
of femoral and brachial arteries from miniature swine, a large animal
species in which we have previously characterized adaptations in
central and peripheral vascular control mechanisms with longer term
training (11, 17, 18).
METHODS Experimental animals. Female Yucatan
miniature swine, 6-8 mo of age, were obtained from the breeder
(Charles River) in two shipments of eight swine. Each shipment was
randomly divided into two groups of four swine. One group of swine
performed exercise training (Trn); the other group remained pen
confined and sedentary (Sed).
Training program. Exercise training
was conducted on a motorized treadmill (Quinton). Swine performed
twice-daily, 1-h bouts of treadmill exercise at 3.5 miles/h over a
period of 7 consecutive days. Exercise performance was rewarded by
feeding at the end of the second daily training bout. Heart weight and
skeletal muscle samples (deltoid and long and lateral heads of triceps
brachii muscles) were obtained for evaluation of training efficacy when swine were killed. Citrate synthase activity, a marker enzyme for
oxidative metabolic capacity, was determined in skeletal muscle samples
according to the method of Srere (22).
Vascular ring preparation. On days of
experiments, swine were preanesthetized with ketamine hydrochloride
(2.25 mg/kg) and then anesthetized with pentobarbital sodium (20 mg/kg). Heparin sodium was administered intravenously (1,000 U/kg).
Swine were then killed by removal of the heart, and segments of femoral
and brachial arteries were immediately dissected from each animal and
placed in chilled (4°C) Krebs bicarbonate buffer solution (see
below). Vessel segments were taken from the same sites in all swine.
Arterial segments were trimmed of fat and connective tissue, without
damaging smooth muscle or endothelium, with the aid of a
stereomicroscope (Zeiss). A total of four vascular rings, 3 mm in axial
length, were cut from each arterial segment. Axial length, outside
diameter, and inside diameter were determined for each vascular ring by
using a calibrated micrometer eyepiece mounted on the stereomicroscope.
One vascular ring of each set of four rings was denuded of endothelium
by gently rubbing its luminal surface with fine-tipped forceps. Minimal
vasorelaxation (i.e., <5%) from a prostaglandin
F2 Length-tension relationship. Femoral
and brachial arterial rings were set to individual optima of their
length-developed tension relationships as described previously (11, 17,
18). Briefly, two stainless steel wires (0.406 mm in diameter) were
passed through the lumen of each vascular ring. One wire was connected
to a force transducer (Grass FT03). The other wire was connected to a
micrometer microdrive (Stoelting), allowing stretching of the vascular
ring by known increments. The vascular ring was submerged in Krebs bicarbonate buffer solution (see below) in a 20-ml tissue bath, equilibrated at 37°C with a 95%
O2-5%
CO2 gas mixture. Isometric tension
development was continuously recorded by using the force transducer and
a computerized data-acquisition system (MacLab).
Vascular rings were stretched to optima of their length-developed
tension relationships by multiple exposures to 60 mM KCl at increasing
amounts of stretch. Stretch was increased in 5 to 10% (of passive
outside diameter) increments. After each exposure to KCl, Krebs
bicarbonate buffer solution was replaced to wash out this
vasocontracting agent. On attainment of optimal stretch, vascular rings
were allowed 1 h for stabilization before further study. All
pharmacological studies were conducted at optimal stretch.
Pharmacological studies.
Concentration-dependent contractile responses of femoral and brachial
arterial rings to norepinephrine (NE) were determined by cumulative
addition of NE to tissue baths (10 Following NE studies, concentration-dependent vasorelaxation responses
to the endothelium-dependent agent BK
(10 Solutions and drugs. Krebs bicarbonate
buffer solution contained (in mM) 131.5 NaCl, 5.0 KCl, 1.2 NaH2PO4,
1.2 MgCl2, 2.5 CaCl2, 11.2 glucose, 13.5 NaHCO3, 0.003 propranolol, and
0.025 EDTA. Propranolol was added to oppose
Concentrated stock solutions of most vasoactive agents were prepared in
distilled water. Stock solutions of indomethacin and A-23187 were
prepared in 95% ethanol and diluted in distilled water before addition
to tissue baths. All agents were purchased from Sigma Chemical.
Statistical analysis. Data are
presented as means ± SE. Heart weight-to-body weight ratios,
citrate synthase activities, and vascular ring characteristics of Sed
and Trn animals were compared by using unpaired
t-tests (23). Two-way analyses of
variance (ANOVAs), with repeated measures on one factor, were used to
compare vasocontractile and vasorelaxation responses of Sed and Trn
vascular rings across the entire range of agent concentrations (i.e.,
comparison of Sed and Trn curves), with Tukey's test employed for post
hoc analysis (23). Before statistical analysis by ANOVA, data for appropriate rings of a given type (e.g., femoral) from an animal were
averaged; thus one animal counted as one observation. Responses to
vasocontracting agents (NE) are expressed in grams of developed tension; that is, tension developed in response to NE, above resting tension due to stretch of the vascular ring. Responses to vasorelaxing agents (BK, A-23187, and SNP) are expressed as relative relaxation from
precontracted levels. Data for relaxation responses to the endothelium-dependent agents BK and A-23187 were included in
statistical analyses only if maximal responses were Concentration of agent inducing 50% of maximal vasocontractile
response was designated the EC50;
conversely, agent concentration producing 50% of maximal
vasorelaxation response was designated the
IC50. Maximal responses to
vasoactive agents were compared between Sed and Trn, as were values for
EC50 or
IC50.
EC50 (or IC50) values were derived by
using nonlinear regression analysis (GraphPad). Unpaired
t-tests (23) were used to compare
maximal responses, as well as EC50
(or IC50) values, between Sed
and Trn. EC50 (or
IC50) values were subjected to
logarithmic transformation before statistical analysis. For all
statistical analyses, P < 0.05 was
considered significant.
RESULTS Physical characteristics. Swine of Sed
and Trn groups were of similar body weights [Sed, 37 ± 3 kg,
n = 7; Trn, 35 ± 1 kg, n = 8; not significant (NS)].
Heart weight-to-body weight ratio tended
(P = 0.06) to be greater in trained
animals (Sed, 4.57 ± 0.19 g/kg; Trn, 4.97 ± 0.15 g/kg). Citrate
synthase activities in the deltoid (Sed, 14.57 ± 0.72; Trn, 16.91 ± 0.68 µmol · min Vascular ring characteristics. Table
1 presents structural characteristics of
vascular rings prepared from femoral and brachial arterial segments.
Dimensions (i.e., outside and inside diameters, axial length) did not
differ between Sed and Trn groups for either femoral or brachial
arterial rings. Wall thickness was also similar between groups for both
femoral (Sed, 0.56 ± 0.03; Trn, 0.62 ± 0.03 mm; NS) and
brachial (Sed, 0.53 ± 0.04; Trn, 0.50 ± 0.03 mm; NS) arterial
vascular rings. In addition, stretch required for optimal tension
development was similar between Sed and Trn animals for both vessel
types, as was resting tension exhibited by vascular rings at optimal
stretch.
Table 1.
Vascular ring characteristics
(PGF2; 3 × 10
5 M) -induced
contraction, elicited by
106 M bradykinin (BK), was
considered to be indicative of effective denudation.
10 to
104 M), as done previously
(11, 17). A recovery period of 90 min was allowed after determination
of responses to NE, permitting reattainment of resting tension by
vascular rings. Krebs bicarbonate buffer solution that bathed vascular
rings was changed every 10 min during this recovery period.
10 to
106 M) and the
endothelium-independent agent sodium nitroprusside (SNP;
1010 to
104 M) were determined, as
done previously (11, 18). Vascular rings were precontracted with
PGF2 (3 × 105 M) to a steady-state
tension 
50% of that exhibited in response to maximal doses
(104 M) of NE. Developed
tension in response to PGF2 was
similar between Sed and Trn for all vasorelaxing agents tested. For
each vessel type (i.e., femoral, brachial) studied, one of the four vascular rings examined from each animal was denuded of its endothelium (see above). In another ring of each vessel type, inhibitors of formation of endothelium-derived nitric oxide [300 µM
NG-nitro-L-arginine
methyl ester (L-NAME)] and
vasodilator prostaglandins (5 µM indomethacin) were present (cf. Ref.
13). These agents were added to tissue baths 30 min before
determination of concentration-dependent responses to BK and SNP. The
remaining two rings of each vessel type were endothelium-intact and
without inhibitor agents. In one of these two rings, relaxation
responses to the calcium ionophore A-23187
(106 M), an
endothelium-dependent vasorelaxing agent, were determined in lieu of
determination of concentration-dependent responses to SNP. Resting
tension was reattained in all vascular rings after determination of
responses to BK; subsequently, responses to SNP (or A-23187) were
determined.
2-adrenergic receptor-mediated vasorelaxation. After equilibration with a 95%
O2-5%
CO2 gas mixture, pH of the buffer
solution was 7.4.
20%.
Satisfaction of this criterion was considered indicative of
preservation of functional endothelium during vascular ring
preparation.
1 · g1)
and long (Sed, 11.69 ± 0.68; Trn, 14.11 ± 0.61 µmol · min1 · g1)
and lateral (Sed, 12.99 ± 1.59; Trn, 17.09 ± 1.58 µmol · min1 · g1)
heads of the triceps brachii muscles were 20-30% greater (all P < 0.05) with training.
Vessel Type
Outer
Diameter, mm
Inner Diameter, mm
Axial
Length, mm
Stretch, %
Resting Tension, g
Femoral
Sed (n = 7)
2.50 ± 0.16
1.39 ± 0.14
2.77 ± 0.20
181 ± 8
5.3 ± 1.7
Trn (n = 8)
2.54 ± 0.11
1.30 ± 0.09
2.92 ± 0.12
182 ± 8
5.6 ± 1.7
Brachial
Sed
(n = 7)
1.84 ± 0.13
0.77 ± 0.11
2.62 ± 0.22
186 ± 9
3.0 ± 0.5
Trn (n = 8)
1.83 ± 0.10
0.84 ± 0.07
2.67 ± 0.26
175 ± 5
3.5 ± 0.7
Values are means ± SE; n, no. of swine. Sed, sedentary
group; Trn, trained group. Stretch refers to increase in outer diameter at which optimal contractile response to 60 mM KCl occurred. Resting tension is that exhibited at optimal stretch, in absence of
vasocontractile agents.
Vasocontractile responses. Figure
1 illustrates contractile responses of
femoral and brachial arterial rings with intact endothelium to
progressively increasing NE concentration. Contractile responses across
the entire range of NE concentrations tested were greater in Trn than
in Sed animals (ANOVA; P < 0.05) for
both vessel types. Maximal responses to NE did not differ between Sed
and Trn groups, however, for either femoral or brachial vascular rings
(Table 2). EC50 values for Trn
were lower than for Sed in both femoral and brachial arterial rings
(P < 0.05; Table
2), indicating greater sensitivity to NE in
Trn compared with Sed.
; n = 8 each) are significantly greater
than those from sedentary group (
;
n = 7 each) across entire range of NE
concentrations tested (P < 0.05).
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Figure 2 illustrates contractile responses
to increasing NE concentration for femoral and brachial vascular rings
denuded of endothelium. Contractile responses in vascular rings from
Trn animals, across the entire range of NE concentrations tested, were
somewhat but insignificantly augmented over those of Sed in both
femoral and brachial arterial rings. Additionally, maximal responses
for Sed and Trn were not different in either femoral or brachial rings
(Table 2). Femoral and brachial arterial rings from Trn swine, however,
exhibited greater sensitivity to NE, as indicated by lower
EC50 values compared with those of
their Sed counterparts (P < 0.05;
Table 2).
;
n = 8 each) are not different from
those from sedentary group (; n = 7 each) across entire range of NE concentrations tested.
Vasorelaxation responses. Figure
3 illustrates relaxation responses to BK of
femoral and brachial arterial rings with intact endothelium, after
precontraction with PGF2.
Relaxation responses across the entire range of BK concentrations
tested were similar for Sed and Trn swine in both vessel types. In
addition, maximal relaxation responses in both femoral and brachial
vascular rings were not different between groups (Table 2).
IC50 values for brachial rings
from Trn were lower than corresponding values for Sed;
IC50 values for femoral rings were
similar between groups (Table 2). Similar findings were obtained when
relaxation responses to BK were determined for femoral and brachial
arterial rings in the presence of inhibitors of nitric oxide
(L-NAME) and vasodilator prostaglandin (indomethacin) formation (Fig.
4). Responses across the entire range of BK
concentrations tested, including maximal responses, were not different
between Sed and Trn animals; however, IC50 values for brachial rings
from Trn swine were lower than those for brachial rings from Sed (Table
2). IC50 values for femoral rings
were similar between groups.
(3 × 105 M) -induced isometric
contraction. Values are means ± SE. Relaxation values are
percentage of developed tension induced by prostaglandin F2 administration. There is no
difference between sedentary () and trained () groups for
responses of femoral rings (n = 6 and
7 for sedentary and trained groups, respectively). Similarly, there is
no difference between sedentary and trained groups for responses of
brachial rings (n = 7 and 8 for
sedentary and trained groups, respectively).
(3 × 105 M) -induced isometric
contraction in presence of blockers of nitric oxide [300 µM
NG-nitro-L-arginine
methyl ester (L-NAME)] and
vasodilator prostaglandin (5 µM indomethacin) formation. Values are
means ± SE. Relaxation values are percentage of developed tension
induced by prostaglandin F2
administration. There is no difference between sedentary () and
trained () groups for responses of femoral rings
(n = 5 and 7 for sedentary and trained
groups, respectively). Similarly, there is no difference between
sedentary and trained groups for responses of brachial rings
(n = 6 and 8 for sedentary and trained groups, respectively).
Figure 5 summarizes the effects of
inhibiting nitric oxide and vasodilator prostaglandin formation on
maximal relaxation responses to BK in femoral and brachial arterial
rings. The presence of L-NAME
and indomethacin in bathing buffer reduced
(P < 0.05) relaxation responses to
106 M BK in femoral
vascular rings from trained swine; otherwise, inhibiting nitric oxide
and vasodilator prostaglandin formation was without significant effect
on maximal relaxation responses to BK.
6 M) from prostaglandin
F2 (3 × 105 M) -induced isometric
contraction. Values are means ± SE. Open bars, sedentary; hatched
bars, trained group. Control, no blockers of nitric oxide and
vasodilator prostaglandin formation present; Indo, indomethacin.
* Response of rings treated with
L-NAME and Indo less than that
of rings not treated with inhibitors
(P < 0.05).
Relaxation responses to a maximally effective dose
(106 M) of the calcium
ionophore A-23187 were also determined. Relaxation of both femoral
(Sed, 86 ± 5; Trn, 72 ± 7%; NS) and brachial (Sed, 66 ± 4;
Trn, 56 ± 6%; NS) arterial rings with intact endothelium were
unchanged with training.
Relaxation responses to SNP after
PGF2-induced contraction are
illustrated in Fig. 6. Across the entire
range of SNP concentrations utilized, relaxation responses of both
femoral and brachial arterial rings were similar in Sed and Trn
animals. Maximal responses obtained were also not different between Sed and Trn for either vessel type (Table 2). Because plateaus in responses
to SNP were not evident for either group in either vessel type, it was
not possible to determine IC50
values for SNP.
(3 × 105 M) -induced isometric
contraction. Values are means ± SE. Relaxation values are
percentage of developed tension induced by prostaglandin F2 administration. There are no
differences between sedentary (; n = 7 each) and trained (; n = 8 each) groups for either femoral or brachial rings.
DISCUSSION
The chief new finding of this study is that short-term, endurance-type exercise training induces adaptations in peripheral arteries. Enhanced responses to NE were exhibited by both femoral and brachial arteries from trained animals. An increased sensitivity to BK was also associated with training but only in brachial arteries. Collectively, our findings and those of Wang and colleagues (26), in coronary arteries of dogs, indicate that even short periods of exercise training can induce vascular adaptations in arteries serving cardiac and skeletal muscle.
Efficacy of training program. Measures of training effectiveness were enhanced by the brief period of training. Heart weight-to-body weight ratio, an index of myocardial hypertrophy in the setting of unchanged body weight, exhibited a tendency to be greater in trained swine; indeed, hypertrophy was about one-half of that previously reported by us in miniature swine trained over a 16- to 20-wk period (11). Citrate synthase activity was greater in several skeletal muscles of trained animals compared with those of their sedentary counterparts. This finding is consistent with findings from a recent study of the effects of a short period of endurance exercise training in humans (21) and with work in rats showing that half time for the training-induced increase in skeletal muscle cytochrome c content is 1 wk (2, 25). Other studies conducted in humans have, however, found no increase in skeletal muscle oxidative capacity with short-term training (e.g., Ref. 7).
Vasorelaxation responses. The primary purpose of this study was to test the hypothesis that endothelium-dependent relaxation responses are augmented by 7 days of exercise training. Enhanced endothelium-dependent vasodilation of canine circumflex coronary arteries has previously been observed after short-term training (26). Whereas the maximal response to the endothelium-dependent agent BK was not altered by training, sensitivity to this agent was greater in brachial arteries from trained animals, as indicated by lower IC50 values (Table 2). Furthermore, this effect of short-term training remained when formation of endothelium-derived nitric oxide and vasodilator prostaglandins were pharmacologically blocked. Thus, although several studies have obtained findings indicative of a training-induced increase in endothelial nitric oxide synthase activity (4, 9, 20, 24), a different mechanism(s) appears to be involved in the increased sensitivity to vasorelaxing effects of BK exhibited by brachial arteries from swine trained for 7 days.
The endothelium-dependent vasorelaxing effect of BK remaining after formation of nitric oxide and vasodilator prostaglandins were inhibited may have been due to endothelium-derived hyperpolarizing factor (EDHF). While the identity of EDHF is controversial (see Ref. 3 for review), EDHF has been implicated in endothelium-dependent relaxation of conduit-type arterial vessels (11, 16). Furthermore, recent work has shown that coronary arteries from exercise-trained dogs exhibit enhanced sensitivity to the vasorelaxing effects of BK, even with inhibited formation of nitric oxide (12). Additional experiments by these investigators showed that enhanced sensitivity to BK, in the presence of nitric oxide synthase inhibition, was associated with greater hyperpolarization of coronary vascular smooth muscle from trained dogs. The findings of Mombouli and colleagues (12) suggest that exercise training increases sensitivity of coronary vascular smooth muscle to EDHF. In the absence of measures of brachial vascular smooth muscle membrane potential, we cannot ascribe our increased sensitivity to BK in the brachial artery to an increase in sensitivity to EDHF. Unchanged sensitivity to BK in the brachial arteries of miniature swine, after longer-term training (11), suggests that other adaptations occur during more prolonged periods of exercise training that render unnecessary increased sensitivity to endothelium-dependent vasorelaxing stimuli (cf. Ref. 10).
It should be emphasized that increased sensitivity to BK was only exhibited by brachial arteries from trained animals. Sensitivity to BK was unchanged in femoral arteries. While the reason(s) for these differing responses to short-term training is unclear, it may be that differences in elevations in blood flow over resting levels (in response to exercise during training bouts) are involved. Blood flows to muscles served by the brachial artery are uniformly elevated two- to threefold in the transition from rest to treadmill running at the speed utilized in our training bouts (1). Blood flows to muscles served by the femoral artery are less uniformly elevated; increases in blood flow to ankle extensors of the miniature swine are particularly modest (1). Thus it may be that the exercise-induced increase in porcine femoral arterial blood flow is less than brachial arterial blood flow. If so, shear stress on vascular endothelium in the femoral artery during training bouts may be insufficient to induce the adaptation(s) resulting in altered sensitivity to BK. It is probable that other, as yet unidentified, factors also contribute to the differing responses to short-term training in the femoral and brachial arteries.
Vasocontractile responses. Both femoral and brachial arterial rings from trained swine exhibited enhanced contractile responses to NE, as well as greater sensitivities to NE. These differences in vascular responses between sedentary and trained animals were less pronounced in vascular rings denuded of their endothelium (Fig. 3 vs. Fig. 2). Nonetheless, EC50 values for denuded vascular rings from trained swine were less than those for rings from sedentary animals (Table 2), again indicating greater sensitivity to the contractile effects of NE. These findings were unexpected, given that we have previously found that arteries isolated from long-term-trained miniature swine (11, 17) exhibit either unchanged or blunted responses to NE. Other groups, however, have reported that exercise training of relatively short duration (i.e., 4-5 wk) enhances in situ vasoconstrictor responses of the circumflex coronary artery to intracoronary administration of NE and phenylephrine in dogs (5, 8). It may be that vasculature of an animal develops a supersensitivity to agents such as NE during the initial portion of a period of endurance exercise training, followed by regression of supersensitivity (11) or even development of blunted responses to adrenergic agents (4, 17) over the longer term. The physiological significance of enhanced responses to NE with short-term training is unknown. Augmented contractile responses to catecholamines would be predicted to reduce blood flow to skeletal muscle during an acute bout of exercise. Furthermore, in the brachial artery, increased sensitivity to endothelium-dependent agonists (and potentially enhanced forelimb muscle blood flow) could be offset by an enhanced response to NE. Additional experiments are required to examine these possibilities.
In summary, the findings of this study indicate that 7 days of endurance exercise training can induce vascular adaptations in arteries serving skeletal muscle of miniature swine. These adaptations include an augmented contractile response and increased sensitivity to NE, and increased sensitivity to BK, a receptor-mediated, endothelium-dependent vasorelaxing agent. The latter adaptation occurs in the brachial, but not femoral, artery and does not appear to involve changes in formation of either endothelium-derived nitric oxide or vasodilator prostaglandins.
ACKNOWLEDGEMENTS
The authors acknowledge the important technical contributions of Shea Klawitter, Gelita Owens, Bill Schrage, Denise Stowers, and Tammy Strawn. Also acknowledged is the critical reading of this manuscript by Dr. Leona Rubin.
FOOTNOTES
Address for reprint requests: R. M. McAllister, Dept. of Veterinary Biomedical Sciences, E102, Veterinary Medicine Bldg., Univ. of Missouri-Columbia, Columbia, MO 65211.
Received 15 August 1996; accepted in final form 30 December 1996.
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