Effects of sprint training on maximal stroke volume of rats with a chronic myocardial infarction.

The hemodynamic response to maximal exercise was determined in rats with a chronic myocardial infarction (MI) that were subjected to 6-8 wk of high-intensity sprint training (HIST) or limited exercise activity (sedentary control). Training was performed 6 days/wk and consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animal's maximal O2 uptake (VO2max). The left ventricular infarct size for the HIST and sedentary control rats was 35 +/- 4 and 34 +/- 3% of the total endocardial circumference, respectively. VO2max was significantly greater for MI rats subjected to the HIST paradigm than for sedentary control rats. This increase in VO2max was due to an increase in the maximal stroke volume that could be generated by the HIST rat during exercise, inasmuch as the maximal heart rate response and the ability to extract O2 from the blood were similar between the two groups of rats. Citrate synthase activities measured in the plantaris muscle of the HIST and sedentary control rats were similar. These results suggest that the increase in VO2max produced with HIST in MI rats may be linked to changes in central cardiac function, as indicated by the increase in maximal stroke volume that could be generated by the MI rat during maximal exercise conditions.     

Thyroid status and response to endothelin-1 in rat arterial vessels

We have previously reported that changes in thyroid status are associated with significant alterations in skeletal muscle blood flow during exercise and that changes in endothelium-dependent vasodilation may contribute to these blood flow abnormalities. The purpose of this study was to test the hypothesis that altered endothelium-dependent vasoconstriction is also associated with changes in thyroid status. To test this hypothesis, rats were rendered hypothyroid with propylthiouracil (Hypo, n = 14) or hyperthyroid with triiodothyronine (Hyper, n = 14) over approximately 3 mo. Treatment efficacy was confirmed by altered (P < 0.05) citrate synthase activity in several hindlimb skeletal muscles from Hypo and Hyper, compared with that in muscles from euthyroid rats (Eut, n = 12). Vascular rings were prepared from abdominal aortae, and responses to several vasoactive agents were determined in vitro. As found previously, maximal acetylcholine-induced vasorelaxation was modulated by thyroid status (Eut, 47 +/- 9; Hypo, 28 +/- 6; Hyper, 68 +/- 5%; P < 0.05). Contractile responses of vascular rings with intact endothelium to the endothelium-derived constrictor endothelin-1 (ET-1), however, were similar among groups across a range of ET-1 concentrations. In addition, maximal responses [Eut, 3.75 +/- 0.47; Hypo, 2.72 +/- 0.25; Hyper, 3.22 +/- 0.42 g; not significant (NS)] and sensitivities (Eut, 8.12 +/- 0.09; Hypo, 8.10 +/- 0.06; Hyper, 8.28 +/- 0.09 -log M; NS) to ET-1 were similar among groups. If these findings from the conduit-type abdominal aorta extend into resistance vasculature, it appears that changes in endothelium-dependent vasoconstriction do not contribute to skeletal muscle blood flow abnormalities associated with thyroid disease states.     

Regional muscle blood flow capacity and exercise hyperemia in high-intensity trained rats

The purpose of this study was to determine the effects of high-intensity treadmill exercise training on 1) the regional distribution of muscle blood flow within and among muscles in rats during high-intensity treadmill exercise (phase I) and 2) on the total and regional hindlimb skeletal muscle blood flow capacities as measured in isolated perfused rat hindquarters during maximal papaverine vasodilation (phase II). Two groups of male Sprague-Dawley rats were trained 5 days/wk for 6 wk with a program consisting of 6 bouts/day of 2.5-min runs at 60 m/min up a 15% grade with 4.5-min rest periods between bouts. After training, blood flows were measured with the radiolabeled microsphere technique (phase I) in pair-weighted sedentary control and exercise-trained rats while they ran at 60 m/min (0% grade). In phase II of the study, regional vascular flow capacities were determined at three perfusion pressures (30, 40, and 50 mmHg) in isolated perfused hindquarters of control and trained rats maximally vasodilated with papaverine. The results indicate that this exercise training program produces increases in the vascular flow capacity of fast-twitch glycolytic muscle tissue of rats. However, these changes were not apparent in the magnitude or distribution of muscle blood flow in conscious rats running at 60 m/min, since blood flows within and among muscles during exercise were the same in trained and control rats.     

Sympathetic neural influences on muscle blood flow in rats during submaximal exercise

These experiments were designed to estimate the involvement of the sympathetic innervation in regulation of hindlimb muscle blood flow distribution among and within muscles during submaximal locomotory exercise in rats. Blood flows to 32 hindlimb muscles and 13 other selected tissues were measured using the radiolabeled microsphere technique, before exercise and at 0.5, 2, 5, and 15 min of treadmill exercise at 15 m/min. The two groups of rats studied were 1) intact control, and 2) acutely sympathectomized (hindlimb sympathectomy accomplished by bilateral section of the lumbar sympathetic chain and its connections to the spinal cord at L2-L3). There were no differences in total hindlimb muscle blood flow among the two groups during preexercise or at 30 s or 2 min of exercise. However, flow was higher in eight individual muscles at 2 min of exercise in the sympathectomized rats. At 5 and 15 min of exercise there was higher total hindlimb muscle blood flow in the denervated group compared with control. These differences were also present in many individual muscles. Our results suggest that 1) sympathetic nerves do not exert a net influence on the initial elevations in muscle blood flow at the beginning of exercise, 2) sympathetic nerves are involved in regulating muscle blood flow during steady-state submaximal exercise in conscious rats, and 3) these changes are seen in muscles of all fiber types.     

Effect of hindlimb unweighting on tissue blood flow in the rat.

The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported (Witzmann et al., J. Appl. Physiol. 54: 1242-1248, 1983) elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow.     

Systemic adenosine deaminase administration does not reduce active hyperemia in running rats

The importance of adenosine in controlling the magnitude and distribution of blood flow among and within skeletal muscles in rats during slow locomotor exercise was tested by systemic infusion of adenosine deaminase (ADA). Blood flows were measured using labeled microspheres before exercise and at 0.5, 15, and 30 min of fast treadmill walking at 15 m/min. An initial infusion of ADA (1,000 U/kg) was given 30 min before the first blood flow measurement and a second injection (1,000 U/kg) was given 5 min into exercise. These infusions maintained ADA activity above 5 U/ml blood throughout the experimental period. This plasma concentration of ADA was shown to be sufficient to result in a 64% decrease in muscle adenosine levels during ischemic contraction. Blood flows were measured in all of the muscles of the hindlimb (28 samples) and in various nonmuscular tissues in ADA-treated and control rats. Preexercise blood flows were primarily directed to slow-twitch muscles and exercise blood flows were highest in muscles with fast-twitch oxidative fibers. ADA treatment did not reduce total muscle blood flow or exercise blood flows in any of the muscles at any time. These findings do not support the hypothesis that adenosine plays an essential role in controlling muscle blood flow in skeletal muscles during normal locomotor activity.     

Sympathetic restraint of muscle blood flow at the onset of dynamic exercise.

Little attention has focused on sympathetic influences on skeletal muscle blood flow at the onset of exercise. We hypothesized that 1) the sympathetic nervous system constrains muscle blood flow and 2) the decline from peak blood flow is mediated by increasing sympathetic vasoconstrictor tone. Mongrel dogs (n = 7) ran on a treadmill after intra-arterial infusion of saline (control) or combined alpha(1)- and alpha(2)-adrenergic blockade (prazosin and rauwolscine). Immediate and rapid increases in hindlimb blood flow occurred at commencement of exercise with peak iliac blood flows averaging 933 +/- 79 and 1,227 +/- 90 ml/min during control and blockade conditions, respectively. At 1 min of exercise, hindlimb blood flow had decreased to 629 +/- 54 and 1,057 +/- 89 ml/min. In the absence of sympathetic vasoconstrictor tone, there was an enhanced peak blood flow at the onset of exercise. In addition, alpha-blockade attenuated the overshoot of hindlimb blood flow compared with the control condition. These data suggest that an immediate and sustained increase in sympathetic outflow restrains hindlimb blood flow at the onset of exercise and is responsible, at least in part, for an overshoot of blood flow to exercising skeletal muscle.     

Progressive elevations in muscle blood flow during prolonged exercise in swine

Distribution of muscle blood flow has not been measured in man during prolonged exercise, but progressive elevations in skin flow coupled with constant cardiac output (QT) have suggested muscle blood flow may be compromised. However, previous experiments with rats demonstrated progressive increases in muscle blood flow over time during prolonged submaximal exercise. The present study was performed to study muscle blood flow in miniature swine during long-term exercise to shed light on this apparent anomaly. QT and distribution of QT were studied with radiolabeled microspheres while pigs ran on a level treadmill at a speed (10.5 km/h) requiring 71 +/- 4% of maximal O2 consumption (VO2 max). QT increased 23% from the 5th to the 30th min of exercise, whereas total skeletal muscle flow increased by 49%. Increases in flow in the muscles resulted from decreased resistance, since mean arterial pressure declined over this time period (-7%). In addition, the proportional increases in muscle flow were similar within synergistic muscle groups independent of fiber type composition (e.g., elbow extensors: 59-78%; elbow flexors: 26-40%). The factor that limited continued exercise appeared to be body temperature. Colonic temperature rose in linear fashion over time; the animals became exhausted at approximately 42 degrees C. These flow data are similar to previous findings in rats and indicate that during prolonged treadmill locomotion in quadrupedal animals muscle blood flow increases over time to near maximal levels.     

Severe exercise alters the strength and mechanisms of the muscle metaboreflex

Previous studies have shown that in dogs performing mild to moderate treadmill exercise, partial graded reductions in hindlimb blood flow cause active skeletal muscle to become ischemic and metabolites to accumulate thus evoking the muscle metaboreflex. This leads to a substantial reflex increase in mean arterial pressure (MAP) mediated almost solely via a rise in cardiac output (CO). However, during severe exercise CO is likely near maximal and thus metaboreflex-mediated increases in MAP may be attenuated. We therefore evoked the metaboreflex via partial graded reductions in hindlimb blood flow in seven dogs during mild, moderate, and severe treadmill exercise. During mild and moderate exercise there was a large rise in CO (1.5 +/- 0.2 and 2.2 +/- 0.3 l/min, respectively), whereas during severe exercise no significant increase in CO occurred. The rise in CO caused a marked pressor response that was significantly attenuated during severe exercise (26.3 +/- 7.0, 33.2 +/- 5.6, and 12.2 +/- 4.8 mmHg, respectively). We conclude that during severe exercise the metaboreflex pressor response mechanisms are altered such that the ability of this reflex to increase CO is abolished, and reduced pressor response occurs only via peripheral vasoconstriction. This shift in mechanisms likely limits the effectiveness of the metaboreflex to increase blood flow to ischemic active skeletal muscle. Furthermore, because the metaboreflex is a flow-raising reflex and not a pressure-raising reflex, it may be most appropriate to describe the metaboreflex magnitude based on its ability to evoke a rise in CO and not a rise in MAP.     

Inspiratory and expiratory muscle perfusion in maximally exercised ponies

The present study was carried out on seven healthy ponies to examine the extent of blood flow in various inspiratory and expiratory muscles at rest and during maximal exertion as well as to determine the proportion of cardiac output needed to perfuse respiratory muscles during these conditions. Tissue blood flow was studied with 15 micron-diameter radionuclide-labeled microspheres injected into the left ventricle during steady conditions. The inspiratory and expiratory muscles comprised 2.41 and 3.05% of body weight, respectively, and received 6.17 and 3.75% of the cardiac output at rest. With maximal exercise, heart rate (from 55 +/- 3 to 218 +/- 4 beats/min), mean aortic pressure (from 125 +/- 5 to 170 +/- 6 mmHg), and cardiac output (from 96 +/- 11 to 730 +/- 78 ml.min-1.kg-1) increased markedly. During exercise blood flow increased significantly in all respiratory muscles (P less than 0.0001) as vascular resistance decreased precipitously. Marked heterogeneity of perfusion existed among various inspiratory as well as expiratory muscles during exercise. Among the inspiratory muscles, the highest perfusion occurred in the diaphragm followed by serratus ventralis, and among the expiratory muscles, the highest perfusion occurred in the internal oblique abdominis and the transverse thoracis (triangularis sterni). Collectively, the inspiratory (8.44%) and expiratory (6.35%) muscle blood flow comprised 14.8 +/- 1.2% of the cardiac output during maximal exercise, a significant increase above resting value, whereas renal fraction of cardiac output decreased from 21% (at rest) to 0.72%.     

Differential sympathetic outflow elicited by active muscle in rats

The present study was undertaken to test the hypothesis that activation of the muscle reflex elicits less sympathetic activation in skeletal muscle than in internal organs. In decerebrate rats, we examined renal and lumbar (mainly innervating hindlimb blood vessels) sympathetic nerve activities (RSNA and LSNA, respectively) during 1 min of 1) repetitive (1- to 4-s stimulation-to-relaxation) contraction of the triceps surae muscle, 2) repetitive tendon stretch, and 3) repetitive contraction with hindlimb circulatory occlusion. During these interventions, RSNA and LSNA responded synchronously as tension developed. The increase was greater in RSNA than in LSNA [+51 +/- 14 vs. +24 +/- 5% (P < 0.05) with contraction, +46 +/- 8 vs. +17 +/- 4% (P < 0.05) with stretch, +76 +/- 20 vs. 39 +/- 7% (P < 0.05) with contraction during occlusion] during all three interventions: repetitive contraction (n = 10, +508 +/- 48 g tension from baseline), tendon stretch (n = 12, +454 +/- 34 g), and contraction during occlusion (n = 9, +473 +/- 33 g). Additionally, hindlimb circulatory occlusion significantly enhanced RSNA and LSNA responses to contraction. These data demonstrate that RSNA responses to muscle contraction and stretch are greater than LSNA responses. We suggest that activation of the muscle afferents induces the differential sympathetic outflow that is directed toward the kidney as opposed to the limbs. This differential outflow contributes to the distribution of cardiac output observed during exercise. We further suggest that as exercise proceeds, muscle metabolites produced in contracting muscle sensitize muscle afferents and enhance sympathetic drive to limbs and renal beds.     

Distribution of blood flow during exercise after blood volume expansion in swine

To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition.     

Muscle pump does not enhance blood flow in exercising skeletal muscle.

The muscle pump theory holds that contraction aids muscle perfusion by emptying the venous circulation, which lowers venous pressure during relaxation and increases the pressure gradient across the muscle. We reasoned that the influence of a reduction in venous pressure could be determined after maximal pharmacological vasodilation, in which the changes in vascular tone would be minimized. Mongrel dogs (n = 7), instrumented for measurement of hindlimb blood flow, ran on a treadmill during continuous intra-arterial infusion of saline or adenosine (15-35 mg/min). Adenosine infusion was initiated at rest to achieve the highest blood flow possible. Peak hindlimb blood flow during exercise increased from baseline by 438 +/- 34 ml/min under saline conditions but decreased by 27 +/- 18 ml/min during adenosine infusion. The absence of an increase in blood flow in the vasodilated limb indicates that any change in venous pressure elicited by the muscle pump was not adequate to elevate hindlimb blood flow. The implication of this finding is that the hyperemic response to exercise is primarily attributable to vasodilation in the skeletal muscle vasculature.     

Determinants of VO2max in rats after high-intensity sprint training

The hemodynamic response to maximal exercise was determined in rats that were subjected to high-intensity sprint training (HIST) and rats that served as sedentary controls. Training consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animals' maximal O2 uptake (VO2max) interspersed with 90 s of rest. Training was performed 6 days/wk for 6 wk. After the training regimen, all rats were acutely instrumented with catheters in the right carotid artery and right ventricle. O2 uptakes, hemodynamic parameters, arterial and mixed venous O2 concentrations, blood gases, and acid-base status were determined at rest and during submaximal and maximal exercise. Results demonstrated that VO2max of HIST rats was significantly greater than that found for sedentary control rats. This increase in VO2max was due to an increase in maximal cardiac output (Qmax), since maximal arteriovenous O2 difference was similar between trained and sedentary rats. The increase in Qmax was due to an increase in maximal stroke volume (SVmax), because maximal heart rate in trained rats was similar to that in sedentary control rats. Citrate synthase and phosphofructokinase activities measured in the white gastrocnemius, plantaris, and soleus muscles of trained and sedentary rats were similar. These results suggest that the increase in VO2max produced with HIST in rats is strongly linked to an increase in central cardiac function as indicated by an increase in Qmax and SVmax.     

Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs

Respiratory muscle blood flow and organ blood flow during endotoxic shock were studied in spontaneously breathing dogs (SB, n = 6) and mechanically ventilated dogs (MV, n = 5) with radiolabeled microspheres. Shock was produced by a 5-min intravenous injection of Escherichia coli endotoxin (0.55:B5, Difco, 10 mg/kg) suspended in saline. Mean arterial blood pressure and cardiac output in the SB group dropped to 59 and 45% of control values, respectively. There was a similar reduction in arterial blood pressure and cardiac output in the MV group. Total respiratory muscle blood flow in the SB group increased significantly from the control value of 51 +/- 4 ml/min (mean +/- SE) to 101 +/- 22 ml/min at 60 min of shock. In the MV group, respiratory muscle perfusion fell from control values of 43 +/- 12 ml/min to 25 +/- 3 ml/min at 60 min of shock. In the SB group, 8.8% of the cardiac output was received by the respiratory muscle during shock in comparison with 1.9% in the MV group. In both groups of dogs, blood flow to most organs was compromised during shock; however, blood flow to the brain, gut, and skeletal muscles was higher in the MV group than in the SB group. Thus by mechanical ventilation a fraction of the cardiac output used by the working respiratory muscles can be made available for perfusion of other organs during endotoxic shock.     

Downhill running: a model of exercise hyperemia in the rat spinotrapezius muscle.

To utilize the rat spinotrapezius muscle as a model to investigate the microcirculatory consequences of exercise training, it is necessary to design an exercise protocol that recruits this muscle. There is evidence that the spinotrapezius is derecruited during standard treadmill exercise protocols performed on the uphill treadmill (i.e., 6 degrees incline). This investigation tested the hypothesis that downhill running would effectively recruit the spinotrapezius muscle as assessed by the presence of an exercise hyperemia response. We used radioactive 15-microm microspheres to determine blood flows in the spinotrapezius and selected hindlimb muscles of female Sprague-Dawley rats at rest and during downhill (i.e., -14 degrees incline; 331 +/- 5 g body wt, n = 7) and level (i.e., 0 degrees incline; 320 +/- 11 g body wt, n = 5) running at 30 m/min. Both level and downhill exercise increased blood flow to all hindlimb muscles (P < 0.01). However, in marked contrast to the absence of a hyperemic response to level running, blood flow to the spinotrapezius muscle increased from 26 +/- 6 ml.min(-1).100 g(-1) at rest to 69 +/- 8 ml.min(-1).100 g(-1) during downhill running (P < 0.01). These findings indicate that downhill running represents an exercise paradigm that recruits the spinotrapezius muscle and thereby constitutes a tenable physiological model for investigating the adaptations induced by exercise training (i.e., the mechanisms of altered microcirculatory control by transmission light microscopy).     

Regional distribution of blood flow during mild dynamic leg exercise in the baboon

Five chair-restrained baboons were trained with operant techniques and a food reward to perform dynamic leg exercise. Cardiac output and blood flows to most tissues were determined by radioactive microsphere distribution. After 2 min of exercise mean arterial blood pressure had increased by 11 +/- 3% (SE), heart rate by 34 +/- 7%, cardiac output by 50 +/- 12%, and O2 consumption by 157 +/- 17%. The blood flow to exercising leg muscle increased by 585 +/- 338% and to the myocardium by 35 +/- 19%. Blood flow to torso and limb skin fell by 38 +/- 4 and 38 +/- 6%, respectively, and similar reductions occurred in adipose tissue blood flow. Nonworking skeletal muscle blood flow decreased by 30 +/- 10%. Renal blood flow was lowered by 16 +/-2%. The lower visceral organs had more variable responses, but when grouped together total splanchnic blood flow fell by 21 +/- 9%. Blood flow to the brain was unchanged with exercise, whereas spinal cord perfusion increased 23 +/- 3%. Thus during short dynamic exercise baboons redistributed blood flow away from skin, fat, nonworking muscles, and visceral organs to supply the needs of exercising muscles. Our data suggest the baboon is a useful animal model for investigating vascular responses of tissues, such as torso skin, adipose, individual visceral organs, and the spinal cord, that cannot be examined in humans.     

Low-intensity training produces muscle adaptations in rats with femoral artery stenosis.

The effectiveness of a mild-intensity exercise program to induce adaptations within skeletal muscle of animals with peripheral arterial insufficiency was evaluated using an isolated perfused hindlimb preparation at a muscle blood flow similar to the peak found in vivo. Adult rats were subjected to bilateral femoral artery stenosis sufficient to limit peak blood flow during exercise but not alter resting blood flow. Stenosed-trained (Sten-Trained) rats walked on a treadmill at an easily achieved speed (20 m/min with a 15% grade) 5 days wk. Exercise tolerance improved from 10 min initially to 2 h/day. Non-stenosed-sedentary (Non-Sten-Sed) and stenosed-sedentary (Sten-Sed) animals were limited to cage activity. Oxygen delivery to the contracting muscles was similar among groups (7.0 +/- 0.4, 7.3 +/- 0.6, and 6.6 +/- 0.6 mumol.min-1.g-1 in Non-Sten-Sed, Sten-Sed, and Sten-Trained, respectively; n = 13 each). Force development was better maintained by Sten-Trained muscle (P less than 0.001) during a sequence of tetanic contraction conditions. Peak oxygen consumption was greater (P less than 0.05) in the Sten-Trained (5.23 +/- 0.34 mumol.min-1.g-1) than in Non-Sten-Sed (4.08 +/- 0.35) and Sten-Sed (4.34 +/- 0.37) rats. The increased peak oxygen extraction (P less than 0.05) by the muscle of the Sten-Trained rats (82.5 +/- 7.1% of oxygen inflow vs. 58.7 +/- 4.7 and 57.4 +/- 5.0%, respectively) was probably related to the increased muscle capillarity and mitochondrial enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: rest and exercise.

In awake dogs, lactic acid was injected into the phrenic and deep circumflex iliac arteries to elicit the diaphragm and abdominal muscle metaboreflexes, respectively. At rest, injections into the phrenic or deep circumflex iliac arteries significantly increased mean arterial blood pressure 21 +/- 7% and reduced cardiac output 6 +/- 2% and blood flow to the hindlimbs 20 +/- 9%. Simultaneously, total systemic, hindlimb, and abdominal expiratory muscle vascular conductances were reduced. These cardiovascular responses were not accompanied by significant changes in the amplitude or timing of the diaphragm electromyogram. During treadmill exercise that increased cardiac output, hindlimb blood flow, and vascular conductance 159 +/- 106, 276 +/- 309, and 299 +/- 90% above resting values, lactic acid injected into the phrenic or deep circumflex iliac arteries also elicited pressor responses and reduced hindlimb blood flow and vascular conductance. Adrenergic receptor blockade at rest eliminated the cardiovascular effects of the respiratory muscle metaboreflex. We conclude that the cardiovascular effects of respiratory muscle metaboreflex activation are similar to those previously reported for limb muscles. When activated via metabolite production, the respiratory muscle metaboreflex may contribute to the increased sympathetic tone and redistribution of blood flow during exercise.     

Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide.

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 +/- 4 vs. 60 +/- 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the l-NAME-treated group: 539 +/- 67 vs. 889 +/- 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.