Comparison between the effect of static contraction and tendon stretch on the discharge of group III and IV muscle afferents.

The exercise pressor reflex is evoked by both mechanical and metabolic stimuli. Tendon stretch does not increase muscle metabolism and therefore is used to investigate the mechanical component of the exercise pressor reflex. An important assumption underlying the use of tendon stretch to study the mechanical component of the exercise pressor reflex is that stretch stimulates the same group III mechanosensitive muscle afferents as does static contraction. We have tested the veracity of this assumption in decerebrated cats by comparing the responses of group III and IV muscle afferents to tendon stretch with those to static contraction. The tension-time indexes as well as the peak tension development for both maneuvers did not significantly differ. We found that static contraction of the triceps surae muscles stimulated 18 of 30 group III afferents and 8 of 11 group IV afferents. Similarly, tendon stretch stimulated 14 of 30 group III afferents and 3 of 11 group IV afferents. However, of the 18 group III afferents that responded to static contraction and the 14 group III afferents that responded to tendon stretch, only 7 responded to both stimuli. On average, the conduction velocities of the 18 group III afferents that responded to static contraction (11.6 +/- 1.6 m/s) were significantly slower (P = 0.03) than those of the 14 group III afferents that responded to tendon stretch (16.7 +/- 1.5 m/s). We have concluded that tendon stretch stimulated a different population of group III mechanosensitive muscle afferents than did static contraction. Although there is some overlap between the two populations of group III mechanosensitive afferents, it is not large, comprising less than half of the group III afferents responding to static contraction.     

Gadolinium attenuates exercise pressor reflex in cats

The exercise pressor reflex, which arises from the contraction-induced stimulation of group III and IV muscle afferents, is widely believed to be evoked by metabolic stimuli signaling a mismatch between blood/oxygen demand and supply in the working muscles. Nevertheless, mechanical stimuli may also play a role in evoking the exercise pressor reflex. To determine this role, we examined the effect of gadolinium, which blocks mechanosensitive channels, on the exercise pressor reflex in both decerebrate and alpha-chloralose-anesthetized cats. We found that gadolinium (10 mM; 1 ml) injected into the femoral artery significantly attenuated the reflex pressor responses to static contraction of the triceps surae muscles and to stretch of the calcaneal (Achilles) tendon. In contrast, gadolinium had no effect on the reflex pressor response to femoral arterial injection of capsaicin (5 microg). In addition, gadolinium significantly attenuated the responses of group III muscle afferents, many of which are mechanically sensitive, to both static contraction and to tendon stretch. Gadolinium, however, had no effect on the responses of group IV muscle afferents, many of which are metabolically sensitive, to either static contraction or to capsaicin injection. We conclude that mechanical stimuli arising in contracting skeletal muscles contribute to the elicitation of the exercise pressor reflex.     

Responses of group III and IV muscle afferents to dynamic exercise

Adreani, Christine M., Janeen M. Hill, and Marc P. Kaufman.Responses of group III and IV muscle afferents to dynamic exercise. J. Appl. Physiol. 82(6):1811-1817, 1997.Tetanic contraction of hindlimb skeletal muscle,induced by electrical stimulation of either ventral roots or peripheralnerves, is well known to activate group III and IV afferents.Nevertheless, the effect of dynamic exercise on the discharge of thesethin fiber afferents is unknown. To shed some light on this question,we recorded in decerebrate cats the discharge of 24 group III and 10 group IV afferents while the mesencephalic locomotor region (MLR) wasstimulated electrically. Each of the 34 afferents had their receptivefields in the triceps surae muscles. Stimulation of the MLR for 1 min caused the triceps surae muscles to contract rhythmically, an effectinduced by an -motoneuron discharge pattern and recruitment orderalmost identical to that occurring during dynamic exercise. Eighteen ofthe 24 group III and 8 of the 10 group IV muscle afferents werestimulated by MLR stimulation. The oxygen consumption of thedynamically exercising triceps surae muscles was increased by 2.5-foldover their resting levels. We conclude that low levels of dynamicexercise stimulate group III and IV muscle afferents.

     

Effect of metabolic products of muscular contraction on discharge of group III and IV afferents

Static muscular contraction has been firmly established to reflexly increase cardiovascular and ventilatory function. Although group III and IV fibers with endings in muscle have been shown to comprise the afferent arm of this reflex arc, little is known about the nature of the contraction-induced stimulus causing the activation of these fibers. This stimulus has often been suggested to be a metabolic product of muscular contraction. We have therefore recorded the impulse activity of group III and IV afferents with endings in the triceps surae muscles of barbiturate-anesthetized cats while we injected into the femoral artery substances believed to be metabolic products of muscular contraction. We found that lithium and sodium lactate (400 mM; 1 ml) had little or no effect on the discharge of group III and IV afferents. Likewise, monobasic sodium phosphate (20 and 400 mM; 1 ml) and 2-chloroadenosine (50-100 micrograms) had only trivial effects on the discharge of these afferents. By contrast, lactic acid (25 and 400 mM; 1 ml) and arachidonic acid (0.5-2.0 mg) caused significant increases in the activity of group III and IV afferents. Most of the excitatory effect of arachidonic acid on the discharge of the afferents was prevented by indomethacin, a cyclooxygenase inhibitor. We conclude that of the substances tested in our experiments, lactic acid and some cyclooxygenase products, such as prostaglandins and thromboxanes, are the most likely to be responsible for any metabolic stimulation of group III and IV afferents during muscular contraction.     

Group III muscle afferents evoke reflex depressor responses to repetitive muscle contractions in rabbits

Repetitive-twitch contraction of the hindlimb muscles in anesthetized rabbits consistently evokes a reflex depressor response, whereas this type of contraction in anesthetized cats evokes a reflex pressor response in about one-half of the preparations tested. Rapidly conducting group III fibers appear to comprise the afferent arm of the reflex arc, evoking the depressor response to twitch contraction in rabbits because electrical stimulation of their axons reflexly decreases arterial pressure. In contrast, electrical stimulation of the axons of slowly conducting group III and group IV afferents reflexly increases arterial pressure in rabbits. In the present study, we examined the discharge properties of group III and IV muscle afferents and found that the former (i.e., 13 of 20), but not the latter (i.e., 0 of 10), were stimulated by 5 min of repetitive-twitch contraction (1 Hz) of the rabbit triceps surae muscles. Moreover, most of the group III afferents responding to contraction appeared to be mechanically sensitive, discharging in synchrony with the muscle twitch. On average, rapidly conducting group III afferents responded for the 5-min duration of 1-Hz repetitive-twitch contraction, whereas slowly conducting group III afferents responded only for the first 2 min of contraction. We conclude that rapidly conducting group III afferents, which are mechanically sensitive, are primarily responsible for evoking the reflex depressor response to repetitive-twitch contractions in anesthetized rabbits.     

Cyclooxygenase blockade attenuates responses of group III and IV muscle afferents to dynamic exercise in cats

Cyclooxygenase products accumulate in statically contracting muscles to stimulate group III and IV afferents. The role played by these products in stimulating thin fiber muscle afferents during dynamic exercise is unknown. Therefore, in decerebrated cats, we recorded the responses of 17 group III and 12 group IV triceps surae muscle afferents to dynamic exercise, evoked by stimulation of the mesencephalic locomotor region. Each afferent was tested while the muscles were freely perfused and while the circulation to the muscles was occluded. The increases in group III and IV afferent activity during dynamic exercise while the circulation to the muscles was occluded were greater than those during exercise while the muscles were freely perfused (P < 0.01). Indomethacin (5 mg/kg iv), a cyclooxygenase blocker, reduced the responses to dynamic exercise of the group III afferents by 42% when the circulation to the triceps surae muscles was occluded (P < 0.001) and by 29% when the circulation was not occluded (P = 0.004). Likewise, indomethacin reduced the responses to dynamic exercise of group IV afferents by 34% when the circulation was occluded (P < 0.001) and by 18% when the circulation was not occluded (P = 0.026). Before indomethacin, the activity of the group IV, but not group III, afferents was significantly higher during postexercise circulatory occlusion than during rest (P < 0.05). After indomethacin, however, group IV activity during postexercise circulatory occlusion was not significantly different from group IV activity during rest. Our data suggest that cyclooxygenase products play a role both in sensitizing group III and IV afferents during exercise and in stimulating group IV afferents during postexercise circulatory occlusion.     

Responses of group III and IV muscle afferents to distension of the peripheral vascular bed.

This study was undertaken to test the hypothesis that group III and IV afferents with endings in skeletal muscle signal the distension of the peripheral vascular network. The responses of these slowly conducting afferents to pharmacologically induced vasodilation and to acute obstruction of the venous drainage of the hindlimbs were studied in barbiturate-anesthetized cats. Afferent impulses arising from endings in the triceps surae muscles were recorded from the L(7) and S(1) dorsal roots. Fifteen of the 48 group IV and 3 of the 19 group III afferents tested were stimulated by intra-aortic injections of papaverine (2-2.5 mg/kg). Sixty-two percent of the afferents that responded to papaverine also responded to isoproterenol (50 microg/kg). Seven of the 36 group IV and 2 of the 12 group III afferents tested were excited by acute distension of the hindlimb venous system. Four of the seven group IV afferents responding to venous distension also responded to papaverine (57 vs. 13% for the nonresponding). Finally, we observed that most of the group IV afferents that were excited by dynamic contractions of the triceps surae muscles also responded either to venous distension or to vasodilatory agents. These results are consistent with the histological findings that a large number of group IV endings have their receptive fields close to the venules and suggest that they can be stimulated by the deformation of these vascular structures when peripheral conductance increases. Moreover, such a mechanism offers the possibility of encoding both the effects of muscle contraction through intramuscular pressure changes and the distension of the venular system, thereby monitoring the activity of the veno-muscular pump.     

Blockade of purinergic 2 receptors attenuates the mechanoreceptor component of the exercise pressor reflex

The finding that pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS), a P2 antagonist, attenuated the pressor response to calcaneal tendon stretch, a purely mechanical stimulus, raises the possibility that P2 receptors sensitize mechanoreceptors to static contraction of the triceps surae muscles. The mechanical component of the exercise pressor reflex, which is evoked by static contraction, can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of this maneuver. During this period of time, group III mechanoreceptors often discharge explosively in response to the sudden tension developed at the onset of contraction. In decerebrated cats, we, therefore, examined the effect of PPADS (10 mg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to contraction and stretch. We found that PPADS significantly attenuated the renal sympathetic response to contraction, with the effect starting 2 s after its onset and continuing throughout its 60-s period. PPADS also significantly attenuated the renal sympathetic nerve response to stretch, but did so after a latency of 10 s. Our findings lead us to conclude that P2 receptors sensitize group III muscle afferents to contraction. The difference in the onset latency between the PPADS-induced attenuation of the renal sympathetic response to contraction and the renal sympathetic response to stretch is probably due to the sensitivities of different populations of group III afferents to ATP released during contraction and stretch.     

Activation of thin-fiber muscle afferents by a P2X agonist in cats.

The responses of group III and IV triceps surae muscle afferents to intra-arterial injection of alpha,beta-methylene ATP (50 microg/kg) was examined in decerebrate cats. We found that this P2X(3) agonist stimulated only three of 18 group III afferents but 7 of 9 group IV afferents (P < 0.004). The three group III afferents stimulated by alpha,beta-methylene ATP conducted impulses below 4 m/s. Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2-receptor antagonist, prevented the stimulation of these afferents by alpha,beta-methylene ATP. We conclude that P2X(3) agonists stimulate only the slowest conducting group III muscle afferents as well as group IV afferents.     

Comparison of the exercise pressor reflex between forelimb and hindlimb muscles in cats

In thirteen cats anesthetized with alpha-chloralose, we compared the cardiovascular and ventilatory responses to both static contraction and tendon stretch of a hindlimb muscle group, the triceps surae, with those to contraction and stretch of a forelimb muscle group, the triceps brachii. Static contraction and stretch of both muscle groups increased mean arterial pressure and heart rate, and the responses were directly proportional to the developed tension. The cardiovascular increases, however, were significantly greater (P < 0.05) when the triceps brachii muscles were contracted or stretched than when the triceps surae muscles were contracted or stretched, even when the tension developed by either maneuver was corrected for muscle weight. Likewise, the ventilatory increases were greater when the triceps brachii muscles were stretched than when the triceps surae muscles were stretched. Contraction of either muscle group did not increase ventilation. Our results suggest that in the anesthetized cat the cardiovascular responses to both static contraction and tendon stretch are greater when arising from forelimb muscles than from hindlimb muscles.     

P2 antagonist PPADS attenuates responses of thin fiber afferents to static contraction and tendon stretch

Injection into the arterial supply of skeletal muscle of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2 receptor antagonist, has been shown previously to attenuate the reflex pressor responses to both static contraction and to tendon stretch. In decerebrated cats, we tested the hypothesis that PPADS attenuated the responses of groups III and IV muscle afferents to static contraction as well as to tendon stretch. We found that injection of PPADS (10 mg/kg) into the popliteal artery attenuated the responses of both group III (n = 16 cats) and group IV afferents (n = 14 cats) to static contraction. Specifically, static contraction before PPADS injection increased the discharge rate of the group III afferents from 0.1 +/- 0.05 to 1.6 +/- 0.5 impulses/s, whereas contraction after PPADS injection increased the discharge of the group III afferents from 0.2 +/- 0.1 to only 1.0 +/- 0.5 impulses/s (P < 0.05). Likewise, static contraction before PPADS injection increased the discharge rate of the group IV afferents from 0.3 +/- 0.1 to 1.0 +/- 0.3 impulses/s, whereas contraction after PPADS injection increased the discharge of the group IV afferents from 0.2 +/- 0.1 to only 0.3 +/- 0.1 impulses/s (P < 0.05). In addition, PPADS significantly attenuated the responses of group III afferents to tendon stretch but had no effect on the responses of group IV afferents. Our findings suggest that both groups III and IV afferents are responsible for evoking the purinergic component of the exercise pressor reflex, whereas only group III afferents are responsible for evoking the purinergic component of the muscle mechanoreflex that is evoked by tendon stretch.     

Different fusimotor reflexes from the ipsi- and contralateral hind limbs of the cat assessed in the same primary muscle spindle afferents

Experiments were performed in forty-five cats anaesthetized with alpha-chloralose. The aim of the study was to investigate a sample of primary muscle spindle afferents from triceps muscle with respect to their fusimotor reflex control from ipsi- as well as contralateral hind limb. Primary muscle spindle afferents of the triceps surae muscle were recorded from the mean rate of firing and the modulation of the afferent response to sinusoidal stretching of the triceps surae muscle was determined. Test measurements were made during tonic stretch of the ipsilateral PBSt, contralateral PBSt, contralateral triceps muscle or during extension of the intact contralateral hind limb. Control measurements were made with ipsi- and contralateral PBSt as well as contralateral triceps muscles relaxed and with contralateral hind limb in resting position. The occurrence and types of fusimotor effects were assessed by comparing test to control responses. The main finding of the present investigation was the great variability in type and size of the fusimotor effects evoked by different ipsi- and contralateral reflex stimuli. Both ipsi- and contralateral stimulations gave rise to predominantly dynamic, predominantly static or mixed static and dynamic fusimotor reflexes. In the same preparation, a given reflex stimulus often caused different reflex responses in different triceps surae primary spindle afferents. In the same afferent unit, different reflex stimuli usually produced fusimotor effects which differed from each other in type and/or size. In general, contralateral whole limb extension and stretch of contralateral PBSt muscles were more potent as reflex stimuli than stretch of the ipsilateral PBSt muscle. Stretch of the contralateral triceps surae muscle was, but for a few afferent units, ineffective as reflexogenic stimulus. It is concluded that the individualized receptive profiles of the primary muscle spindle afferents, which have been postulated in earlier investigations where the effects of different stimuli have been investigated on different cell populations, still seems to hold good when the stimuli are tested on the same units. The individuality of the receptive profiles of gamma-motoneurones is discussed in relation to different motor control hypotheses.     

Increasing gracilis muscle interstitial potassium concentrations stimulate group III and IV afferents

Static muscular contraction reflexly increases arterial blood pressure and heart rate. One possible mechanism evoking this reflex is that potassium accumulates in the interstitial space of a working muscle to stimulate group III and IV afferents whose activation in turn evokes a pressor response. The responses of group III and IV muscle afferents to increases in interstitial potassium concentrations within the range evoked by static contraction are unknown. Thus we injected potassium chloride into the gracilis artery of anesthetized dogs while we measured both gracilis muscle interstitial potassium concentrations with potassium-selective electrodes and the impulse activity of afferents in the gracilis nerve. We found that increasing interstitial potassium concentrations to levels similar to those seen during static contraction stimulated 14 of 16 group III and 29 of 31 group IV afferents. The responses of the afferents to potassium were concentration dependent. The typical response to potassium consisted of a burst of impulses, an effect that returned to control firing rates within 26 s, even though interstitial potassium concentrations remained elevated for several minutes. Although our results suggest that potassium may play a role in initiating the reflex cardiovascular responses to static muscular contraction, the accumulation of this ion does not appear to be solely responsible for maintaining the pressor response for the duration of the contraction.     

Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction

The renal vasoconstriction induced by the sympathetic outflow during exercise serves to direct blood flow from the kidney toward the exercising muscles. The renal circulation seems to be particularly important in this regard, because it receives a substantial part of the cardiac output, which in resting humans has been estimated to be 20%. The role of group III mechanoreceptors in causing the reflex renal sympathetic response to static contraction remains an open question. To shed some light on this question, we recorded the renal sympathetic nerve responses to static contraction before and after injection of gadolinium into the arterial supply of the statically contracting triceps surae muscles of decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been shown to be a selective blocker of mechanogated channels in thin-fiber muscle afferents, which comprise the afferent arm of the exercise pressor reflex arc. In decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and pressor responses to static contraction (60 s) after a latent period of 60 min; both responses recovered after a latent period of 120 min. We conclude that thin-fiber mechanoreceptors supplying contracting muscle are involved in some of the renal vasoconstriction evoked by the exercise pressor reflex.     

Attenuation of reflex pressor and ventilatory responses to static muscular contraction by intrathecal opioids

We have tested the hypothesis that intrathecal injections of opioid peptides attenuate the reflex pressor and ventilatory responses to static contraction of the triceps surae muscles of chloralose-anesthetized cats. We found that before intrathecal injections of [D-Ala2]Met-enkephalinamide (100 micrograms in 0.2 ml), static contraction increased mean arterial pressure and ventilation by 32 +/- 5 (SE) mmHg and 227 +/- 61 (SE) ml/min, whereas after injection of this opioid peptide, static contraction increased mean arterial pressure and ventilation by only 15 +/- 5 mmHg and 37 +/- 33 ml/min, respectively. The attenuation of both the pressor and ventilatory responses to static contraction by [D-Ala2]Met-enkephalinamide were statistically significant (P less than 0.05). Moreover, the attenuation was probably not caused by an opioid-induced withdrawal of sympathetic outflow because [D-Ala2]Met-enkephalinamide had no effect on the pressor and ventilatory responses evoked by high-intensity electrical stimulation of the central cut end of the sciatic nerve. In addition, intrathecal injection of peptides that were highly selective agonists for either the opioid mu- or delta-receptor attenuated the reflex responses to static contraction. Naloxone (1,000 micrograms), injected intrathecally, prevented the attenuation of the reflex responses to contraction by opioid peptides. We speculate that the opioid-induced attenuation of the reflex pressor and ventilatory responses to static contraction may have been due to suppression of substance P release from group III and IV muscle afferents.     

Role played by acid-sensitive ion channels in evoking the exercise pressor reflex

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half (P<0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.     

Acid-sensing ion and epithelial sodium channels do not contribute to the mechanoreceptor component of the exercise pressor reflex

Amiloride, injected into the popliteal artery, has been reported to attenuate the reflex pressor response to static contraction of the triceps surae muscles. Both mechanical and metabolic stimuli arising in contracting skeletal muscle are believed to evoke this effect, which has been named the exercise pressor reflex. Amiloride blocks both acid-sensing ion channels, as well as epithelial sodium channels. Nevertheless, amiloride is thought to block the metabolic stimulus to the reflex, because this agent has been shown to attenuate the reflex pressor response to injection of lactic acid into the arterial supply of skeletal muscle. The possibility exists, however, that amiloride may also block mechanical stimuli evoking the exercise pressor reflex. The mechanical component of the reflex can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of contraction. During this period of time, the sudden tension developed by contraction onset briskly discharges mechanoreceptors, whereas it has little effect on the discharge of metaboreceptors. We, therefore, examined the effect of amiloride (0.5 microg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to static contraction of the triceps surae muscles in decerebrated cats. We found that amiloride significantly attenuated the pressor and renal sympathetic responses to contraction; for the latter variable, the attenuation started 10 s after the onset of contraction. Our findings lead us to conclude that acid-sensing ion channels and epithelial sodium channels play little, if any, role in evoking the mechanical component of the exercise pressor reflex.     

Role played by purinergic receptors on muscle afferents in evoking the exercise pressor reflex.

The exercise pressor reflex is believed to be evoked, in part, by multiple metabolic stimuli that are generated when blood supply to exercising muscles is inadequate to meet metabolic demand. Recently, ATP, which is a P2 receptor agonist, has been suggested to be one of the metabolic stimuli evoking this reflex. We therefore tested the hypothesis that blockade of P2 receptors within contracting skeletal muscle attenuated the exercise pressor reflex in decerebrate cats. We found that popliteal arterial injection of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg), a P2 receptor antagonist, attenuated the pressor response to static contraction of the triceps surae muscles. Specifically, the pressor response to contraction before PPADS averaged 36 +/- 3 mmHg, whereas afterward it averaged 14 +/- 3 mmHg (P < 0.001; n = 19). In addition, PPADS attenuated the pressor response to postcontraction circulatory occlusion (P < 0.01; n = 11). In contrast, popliteal arterial injection of CGS-15943 (250 micro g/kg), a P1 receptor antagonist, had no effect on the pressor response to static contraction of the triceps surae muscles. In addition, popliteal arterial injection of PPADS but not CGS-15943 attenuated the pressor response to stretch of the calcaneal (Achilles) tendon. We conclude that P2 receptors on the endings of thin fiber muscle afferents play a role in evoking both the metabolic and mechanoreceptor components of the exercise pressor reflex.     

MLR stimulation and exercise pressor reflex activate different renal sympathetic fibers in decerebrate cats.

Although mesencephalic locomotor region (MLR) stimulation and the exercise pressor reflex have been shown to increase whole nerve renal sympathetic activity, it is not known whether these mechanisms converge onto the same population of renal sympathetic postganglionic efferents. In decerebrate cats, we examined the responses of single renal sympathetic postganglionic efferents to stimulation of the MLR and the exercise pressor reflex (i.e., static contraction of the triceps surae muscles). We found that, in most instances (24 of 28 fibers), either MLR stimulation or the muscle reflex, but not both, increased the discharge of renal postganglionic sympathetic efferents. In addition, we found that renal sympathetic efferents that responded to static contraction while the muscles were freely perfused responded more vigorously to static contraction during circulatory arrest. Moreover, stretch of the calcaneal (Achilles) tendon stimulated the same renal sympathetic efferents as did static contraction. These findings suggest that MLR stimulation and the exercise pressor reflex do not converge onto the same renal sympathetic postganglionic efferents.     

Bradykinin release from contracting skeletal muscle of the cat

Results of previous studies from our laboratory suggest that bradykinin has a role in the exercise pressor reflex elicited by static muscle contraction. The purpose of this study was to quantify the release of bradykinin from contracting skeletal muscle. In 18 cats, blood samples were withdrawn directly from the venous effluent of the triceps surae muscles immediately before and after 30 s of static contraction producing peak muscle tensions of 33, 50, and 100% of maximum electrically stimulated contraction. Contractions producing muscle tensions of 50 and 100% of maximum increased muscle venous bradykinin levels by 27 +/- 9 and 19 +/- 10 pg/ml, respectively. Conversely, 33% maximum contraction did not alter muscle venous bradykinin concentrations. However, when captopril was administered to slow the degradation of bradykinin, muscle venous bradykinin increased from 68 +/- 15 pg/ml at rest to 106 +/- 18 after contractions of 33% of maximum. When muscle ischemia was induced by 2 min of arterial occlusion before and during 30 s of 33% of maximum contraction, muscle venous bradykinin increased by 15 +/- 5 pg/ml. In addition, contraction-induced changes in muscle venous pH and lactate strongly correlated with bradykinin concentrations (r = 0.80 and 0.83, respectively). These data demonstrate that static contraction of relatively high intensity evokes the release of bradykinin from skeletal muscle and that ischemia, decreased pH, and increased lactate are strongly correlated with this release.