PubMed HealthSearch

SEARCH · PubMed Health

Results for “Hindlimb”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Flow-induced oxygen uptake by the perfused rat hindlimb is inhibited by vasodilators and augmented by norepinephrine: a possible role for the microvasculature in hindlimb thermogenesis.

Oxygen uptake in the perfused rat hindlimb was studied at 25 degrees C using an artificial perfusate, and the effects of perfusate flow rate, norepinephrine, and vasodilators were compared. Hindlimb oxygen uptake and perfusion pressure each increased as the flow rate was increased stepwise from 2 to 18.5 mL/min per hindlimb. At each flow rate, the rate of oxygen uptake was inhibited by the vasodilator nitroprusside (0.5 mM) and increased by norepinephrine (5 nM). A corresponding change in perfusion pressure also occurred, with norepinephrine leading to a marked increase and nitroprusside leading to a decrease; however, changes in oxygen uptake and pressure were not linearly related. The lactate/pyruvate ratio of the perfusate was used as an index of tissue perfusion and was determined at each flow rate. Lactate and pyruvate efflux increased as the flow rate was increased stepwise from 2 to 18.5 mL/min per hindlimb. At 2 mL/min per hindlimb, the lactate/pyruvate ratio was 15; at flow rates equal or greater than 4 mL/min per hindlimb, the ratio was constant at 9. Nitroprusside had no significant effect on the ratio at any flow rate even though a marked inhibitory effect on oxygen uptake was evident. Muscle content of high energy phosphates at 8 mL/min per hindlimb did not differ before and after treatment with vasodilators. In addition, the vasodilators had no apparent effect on skeletal muscle oxygen uptake or force development during electrical stimulation. The findings indicate that oxygen uptake by the hindlimb is not limited by inadequate perfusion and that oxygen uptake can be further increased by norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

A peripheral 5-HT1D-like receptor involved in serotonergic induced hindlimb scratching in rats.

The pharmacological characteristics of hindlimb scratching induced by serotonergic compounds were studied. We conclude that hindlimb scratching induced by serotonergic compounds is mediated by a serotonin1D (5-HT1D) or 5-HT1D-like receptor outside the blood-brain barrier because hindlimb scratching could be induced by s.c. injection of 5-methoxytryptamine (5-MeOT), 5-carboxamidotryptamine (5-CT), bufotenine, 5-hydroxytryptamine (5-HT) and tryptamine. These compounds have high affinity for 5-HT1A and 5-HT1D receptors. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C receptor agonist MK 212, and the mixed 5-HT1C/5-HT2 receptor agonists (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and quipazine did not induce hindlimb scratching. Rather, the latter compounds attenuated 5-MeOT-induced hindlimb scratching. The 5-HT releasing compounds fenfluramine and p-chloroamphetamine (PCA) inhibited whereas the 5-HT re-uptake inhibitors fluvoxamine and indalpine potentiated 5-MeOT-induced hindlimb scratching. 5-MeOT-induced hindlimb scratching could be inhibited dose dependently by the alpha 2-adrenoceptor blockers yohimbine and rauwolsince, which also have high affinity for 5-HT1D receptors, whereas the alpha 2-adrenoceptor blocker piperoxan only weakly counteracted hindlimb scratching. Haloperidol, apomorphine, morphine, clonidine and methiothepin strongly attenuated hindlimb scratching, atropine, naloxone and ICS 205930 attenuated it weakly whereas domperidone, methylatropine and mepyramine were inactive in doses up to 10 mg/kg. Hindlimb scratching induced by 5-MeOT was potentiated by the 5-HT receptor antagonists metergoline, methysergide, mesulergine, mianserin, ritanserin and xylamidine. Hindlimb scratching was not induced by i.c.v. injection of 5-MeOT.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine

Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs.

1. The contribution of endogenous adenosine to the increase in hindlimb blood flow that occurs during treadmill exercise was evaluated in conscious dogs. We postulated that if adenosine is essential for the hindlimb hyperaemic response, then pharmacological treatment of the animals with adenosine receptor antagonists should decrease hindlimb blood flow during treadmill exercise. 2. A total of twenty-three dogs were chronically instrumented for measurement of aortic blood pressure and hindlimb blood flow using electromagnetic or Doppler flow probes on the left external iliac artery. Measurements of arterial blood pressure, hindlimb blood flow and heart rate were made during steady-state treadmill exercise in both the presence and the absence of adenosine receptor antagonists. Four different protocols were performed using different routes of administration of two adenosine receptor antagonists. Aminophylline was used in most of the experiments, and the effects of the more potent antagonist, 8-phenyltheophylline, were also evaluated. In addition, the dogs exercised at varying intensities ranging from a low level of 5.5 km h-1 at 0% gradient to a high intensity of 5.5 km h-1 at 21% gradient. 3. Aminophylline given as a single intravenous dose, or as a constant infusion either intravenously or directly into the hindlimb artery, did not decrease hindlimb blood flow at low, moderate or high intensities of exercise. Likewise, the blockade of adenosine receptors with 8-phenyltheophylline, given systemically or as a bolus injection administered directly into the hindlimb circulation during moderate exercise, did not attenuate the hindlimb blood flow response. 4. Our data demonstrate that exercise hyperaemia of the hindlimb is not reduced by antagonism of adenosine receptors. These findings are consistent with the hypothesis that adenosine is not an essential mediator of hindlimb vasodilatation during exercise.

Adenosine

Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: functional aspects.

Following heterotopic transplantation of the thoracic neural tube to the lumbar region on embryonic day (E) 2, the transplanted cord differentiates normally and establishes neuroanatomical connections with the host central nervous system and hindlimb muscles. Beginning on about E12, however, the neuromuscular system begins to undergo regressive changes resulting in motoneuron degeneration and muscle atrophy (O'Brien and Oppenheim, 1990). In the present paper, we have examined the development of neuromuscular function in thoracic transplant embryos from E6 to the time of hatching on E20-21. The onset of hindlimb movements and reflexes occurred at the same time (E6-E8) in both control and thoracic transplant embryos. Further, both the nature (pattern) and frequency of these movements appeared normal in the thoracic transplants up to E10-E12, after which there was a gradual and marked reduction in the frequency, and an alteration in the pattern, of both spontaneous and reflex-evoked hindlimb movements. After E16 normal movements were virtually absent in many of the thoracic transplant cases. By contrast, movements of the head, trunk and wings were normal in these embryos throughout the observation period. Hindlimbs innervated partly by the thoracic transplant and partly by remaining host lumbar cord did not exhibit the regressive changes in function after E10 that occurred in hindlimbs innervated exclusively by the thoracic transplant. EMG recordings from specific hindlimb muscles innervated solely by thoracic motoneurons demonstrated that the activation pattern of both flexors and extensors was similar to the repetitive pattern observed in normal thoracically innervated intercostal muscles (i.e., extensor-like). Muscles did not show distinguishable EMG burst patterns with inhibitory periods as do control lumbar innervated muscles. We conclude that the development of the pattern generating circuitry in the transplanted thoracic cord was similar to normal thoracic cord and thus appeared to be uninfluenced by having contacted the foreign hindlimb muscle targets early in development. Activity blockade with curare from E6 to E14 suppressed the loss of motoneurons that occurs in the thoracic transplant after E10. Thus, the abnormal thoracic-like activation pattern of thoracically innervated hindlimbs may be a critical signal in the initiation of the neuromuscular regression that occurs after E10 in these preparations. Finally, although the innervation and formation of neuromuscular endplates in thoracic transplants appeared normal up to E12, by E14 both the intramuscular nerves and the endplates exhibited signs of degeneration and regression. Thoracic motoneurons are initially able to innervate and functionally activate hindlimb muscles in a manner similar to that of thoracically innervated intercostal muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Geometry of blood-tissue exchange in bat flight muscle compared with bat hindlimb and rat soleus muscle.

We investigated the relationship between capillary-to-fiber geometry and muscle aerobic capacity by comparing the bat flight muscle (pectoralis muscle), i.e., an ultimate case of extreme O2 demand in a mammalian skeletal muscle, with bat hindlimb and rat soleus muscles. At a given sarcomere length (2.1 microns), fiber cross-sectional area was considerably smaller in bat muscles (pectoralis 318 +/- 10 microns 2, hindlimb 447 +/- 35 microns 2) than in rat soleus muscle (2,027 +/- 125 microns 2). Capillary number per fiber cross-sectional area was much greater in bat pectoralis (6,394 +/- 380/mm2) than in bat hindlimb and rat soleus muscle (2,865 +/- 238 and 1,301 +/- 129/mm2, respectively; all values normalized to 2.1-microns sarcomere length). At the same sarcomere length (2.1 microns), the degree of tortuosity and branching of capillaries were significantly greater in bat pectoralis than in bat hindlimb and rat soleus muscle. In bat flight muscle, capillary length per fiber volume was very high (9,025 +/- 342/mm2). It was 2.2- and 5.4-fold larger than in bat hindlimb and rat soleus, respectively. Mitochondria occupied 35.3 +/- 1.2, 16.5 +/- 1.3, and 6.1 +/- 0.9% of the muscle fiber volume in bat pectoralis, hindlimb, and rat soleus muscles, respectively. There was a strong correlation between capillary length (as well as capillary surface) per fiber volume and mitochondrial volume density in all muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis, we found that 1) the number of capillaries around a fiber was linearly related to mitochondrial volume per micron length of fiber in the muscles but that 2) capillary surface per fiber surface, at given mitochondrial volume per micron length of fiber, was about twice as large in bat pectoralis as in rat soleus muscle, whereas in bat hindlimb it was intermediate between that in bat pectoralis and that in rat soleus muscle. This was due to the differences in fiber size (rat soleus greater than bat muscles) and capillary-to-fiber ratio (bat pectoralis greater than hindlimb) between the muscles. It is notable that in the bat, the substantially greater O2 transfer capacity of the flight muscle compared with hindlimb was achieved by increasing the size of the capillary-to-fiber interface, i.e., capillary-to-fiber surface, via an increase in capillary number rather than by substantially reducing fiber size.

Animals

Hindlimb proportions, allometry, and biomechanics in Old World monkeys (primates, Cercopithecidae).

The traditional focus on morphological rather than mechanical units has obscured some significant functional differences in the hindlimbs of primates. This paper examines the allometric and biomechanical basis for some distinctive proportional differences among pairs of morphological units in the hindlimb, and especially the foot, of cercopithecid primates. Five major conclusions are reached. First, many hindlimb dimensions scale allometrically with body mass to maintain mechanical similarity within taxonomic and locomotor groups. Therefore, the majority of traditional indices which describe the shape of the foot within cercopithecids reveal differences which are primarily a function of size. Second, the hindlimb segments in colobines, and especially in Presbytis, are relatively long, probably to enhance leaping. Third, the major distinction of terrestrial cercopithecines among the features analysed is reduction in the length of the phalanges, due to the reduced importance of grasping during locomotion and the assumption of digitigrady. Fourth, Theropithecus and male Erythrocebus have high crural indices, relative to their body masses, which can facilitate curosoriality. Female E. patas already has a high crural index as a function of its body mass. Fifth, macaques form a distinctive group among cercopithecines, characterized by relatively short hindlimbs. Relatively very short hindlimbs in Macaca fuscata and M. thibetana suggest that climatic conditions can have an added effect on the lengths of the hindlimb segments. In summary, this analysis of the lengths of the hindlimb segments relative to body size reveals taxonomic differences which are due in part to phylogeny, to differences in locomotor behavior, and to substrate use.

Analysis of Variance

Neuromuscular specificity following cross-stage hindlimb transplantation.

In order to determine whether spinal motoneurons can regenerate to their proper targets at stages beyond those when such specificity is typically expressed, autologous and homologous (same- and cross-stage) hindlimb transplantations were performed using bullfrog tadpoles (Rana catesbeiana). Neuromuscular specificity was assessed by applying horseradish peroxidase to the ventral thigh of the transplanted hindlimb and mapping the locations of retrogradely labeled motoneurons. Previously, we found that the hindlimb was reinnervated normally in young tadpoles whose motor nerves were transected. However, motor axons in older animals showed no evidence of target specificity when reinnervating the tadpole's own limb. In the present study, innervation was normal in young tadpoles whose hindlimb was removed and replaced in its original position. Axons of older hosts innervating hindlimbs transplanted from young tadpoles distinguished flexor from extensor limb regions, but failed to distinguish thigh from shank, demonstrating that axons in older animals can respond to at least some guidance cues. The lack of specificity along the proximal-distal axis appears to be a consequence of homologous transplantation since limbs transplanted from one young tadpole to another showed the same loss of proximal-distal specificity. One possibility is that the shank degenerates when the hindlimb is transplanted to a different host. Shank motoneurons, lacking their proper target, may then innervate the thigh. However, shank motoneurons did not innervate the thigh when motor nerve transection was combined with amputation of the hindlimb just above the presumptive knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Influence of single hindlimb support during simulated weightlessness in the rat.

Mature male rats (n = 16) were assigned to either 14 days of head-down suspension with one hindlimb supported (HDS) or to control cages (C) of similar dimensions. Hindlimb support during HDS preserved the muscle mass-to-body mass ratio (mg/100g) compared with C conditions for the soleus (48.3 +/- 1.0 to 41.7 +/- 1.0), plantaris (98.4 +/- 3.4 to 103.3 +/- 4.1), and gastrocnemius (484.7 +/- 18.5 to 507.2 +/- 13.9). However, the muscle mass-to-body mass ratio was significantly lower for the soleus (28.9 +/- 1.5), plantaris (83.9 +/- 3.6), and gastrocnemius (411.9 +/- 24.2) muscles from the freely hanging hindlimbs compared with the contralateral muscles from the supported hindlimbs or muscles from C animals. Citrate synthase activity (mumol.g-1.min-1) was significantly lower in soleus muscles from HDS rats in both the supported (19.4 +/- 2.3) and freely hanging (20.0 +/- 1.6) hindlimbs compared with C (28.5 +/- 3.1), whereas soleus muscle glycogen concentration (mg/g) was significantly higher in the freely hanging limbs from HDS rats (5.90 +/- 0.31) but not in the supported limbs (3.80 +/- 0.61) compared with C (4.34 +/- 0.50). Doppler flow probes were used to determine that iliac blood flow to freely hanging hindlimbs was significantly decreased after 48 (-19 +/- 5%) and 72 (-20 +/- 6%)h of HDS compared with presuspension values. In addition, iliac vascular resistance was significantly elevated at most time points during the 72 h of HDS in the freely hanging limbs but not the supported hindlimbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The interaction of vasodilating drugs and sympathetic blockade in normal and ischemic canine hindlimbs.

The purpose of this study was to determine if intraarterial vasodilating drugs could augment the vasodilation produced by sympathetic blockade, such as occurs during epidural anesthesia. Papaverine (2 mg/min), nitroglycerin (1 microgram/kg/min), aand saline were infused into the femoral artery before and after lumbar sympathectomy in six arterially isolated canine hindlimbs. Femoral blood flow was controlled with a perfusion circuit at baseline (80 ml/min), half-baseline (40 ml/min), and low (5 ml/min) flow rates so that hindlimb mean arterial pressure served as an index of peripheral vasodilation. At low flow, hindlimb arteriovenous oxygen content difference increased from 1.4 (baseline) to 6.2 ml O2/dl, consistent with peripheral ischemia. At baseline flow before sympathectomy, papaverine and nitroglycerin caused a decrease in hindlimb mean arterial pressure of 30% and 18%, respectively (p less than 0.01 vs saline control), equivalent to the decreases of 31% and 16% after sympathectomy (p less than 0.01). At half-baseline, papaverine and nitroglycerin reduced hindlimb mean arterial pressure by 22% and 12%, respectively (p less than 0.01), and caused comparable vasodilation after sympathectomy. Neither drug significantly changed hindlimb mean arterial pressure at low flow. Sympathectomy itself reduced hindlimb mean arterial pressure by 23% at baseline flow (p less than 0.01), by 18% at half-baseline flow (p less than 0.01), but had no effect at low flow. We conclude that intraarterial papaverine and nitroglycerin cause peripheral vasodilation that is synergistic with sympathectomy-induced adrenergic blockade, but they cannot augment vasodilation caused by peripheral ischemia.

Anesthesia, Epidural

Area specific reflexes from normal and supernumerary hindlimbs of Xenopus laevis.

Two area specific reflexes elicited by natural stimulation of different regions of the hindlimbs of Xenopus laevis have been identified. Light or intense mechanical stimulation of the foot evokes reflex activity in the ipsilateral knee flexor nerve; moderate pressure applied to the calf evokes reflex activity predominantly in the ipsilateral knee extensor nerve. The reflex responses have been recorded electrophysiologically to overcome the limitations of behavioral observations for determining the presence of activity in particular muscles. Normal area specific reflexes are elicited in the normal ipsilateral hindlimb by stimulation of grafted supernumerary hindlimbs innervated either by hindlimb (lumbar) or by non-limb (thoracic) spinal cord segments. The area specific reflexes can be elicited only if the limb is grafted to a host younger than stage 54-55 of Nieuwkoop and Faber ('56), the stage at which reflex movements are first observed behaviorally. Abnormal reflex responses are evoked by stimulation of supernumerary limbs innervated by either thoracic or lumbar segments when the limb buds are grafted to older larvae. Supernumerary forelimbs grafted at early stages and innervated by either thoracic or lumbar spinal cord segments generally fail to elicit area specific reflex responses in the normal hindlimb. Single-unit recordings of afferent fibers supplying the normal and supernumerary hindlimbs show that each limb receives a separate nerve supply. No evidence for branched afferent fibers has been found. The implications of these results for theories of neuronal specification are discussed, particularly the hypothesis that peripheral tissues are able to specify the central actions of afferent fibers that innervate them.

Animals

Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: anatomical aspects.

Thoracic spinal cord transplanted to the lumbar region at the time of neural tube closure in the chick embryo survives and initially differentiates normally similar to in situ thoracic cord. Normal numbers of motoneurons are produced that innervate the host hindlimb musculature. In control thoracic cord approximately 70% of the motoneurons are lost by normal cell death between embryonic day (E) 6 and E11-E12. By contrast, the transplanted thoracic cord loses only about 30% of the motoneurons during this period. Transplantation of one hindlimb to the thoracic region also reduces the normal loss of in situ thoracic motoneurons. We conclude that some factor(s) associated with the increased target size provided by the hindlimbs promotes the survival of thoracic motoneurons. In contrast, by E16-E18 motoneuron numbers in the thoracic transplants decrease to below control levels. Dorsal root ganglion cells in the transplant were also initially increased (on E8) but later decreased to below control values. Hindlimb muscles innervated by thoracic motoneurons in the transplant also differentiated normally up to E10 to E12. Myotube size and numbers, muscle size and myotube types (fast versus slow) all developed normally in several thoracically-innervated hindlimb muscles. However, beginning on E14 myotube numbers and muscle size were markedly decreased resulting in muscle atrophy. Injections of horseradish peroxidase (HRP) into the thoracic transplants labelled neurons in the host spinal cord and brainstem rostral to the transplant thereby indicating an anatomical continuity between host and transplant neural tube. Injections of HRP into specific thoracically innervated hindlimb muscles on E8 labelled distinct pools of motoneurons in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Functional organization of the nociceptive withdrawal reflexes. I. Activation of hindlimb muscles in the rat.

1. The organization of the nociceptive hindlimb withdrawal reflexes was investigated in 93 halothane/nitrous oxide anesthetized rats. Electromyographical techniques were used to record reflex activity in single motor units. 2. Most of the hindlimb muscles were activated by noxious mechanical stimulation of the skin of the ipsilateral hindlimb. These were the plantar flexors of the digits, the pronators of the paw, the dorsiflexors and the plantar flexors of the ankle, the flexors of the knee, the flexors of the hip and the adductors. By grading the stimulus intensity it was shown that all these muscles received input from cutaneous nociceptors. 3. Noxious stimulation of the skin failed to activate the obturator, knee extensors and m. tibialis posterior and, in most rats tested, m. semimembranosus and m. adductor magnus. The plantar flexors of the ankle, while exhibiting a clear nocireceptive field in all rats tested, had a high threshold and responded much more weakly than the dorsiflexors of the ankle. Thus, responses in muscles which oppose gravity in the standing position were either very weak or absent. 4. The present study shows that each of the activated hindlimb muscles has a highly organized nocireceptive field on the skin, which is related to the withdrawal movement caused by the muscle itself. Each of the muscles normally causes the withdrawal of its receptive field when the foot is on the ground. The skin area most effectively withdrawn, in this situation, corresponds to the most sensitive area of the nocireceptive field. However, with the exception of the plantar flexors of the digits and/or the ankle, each of the hindlimb muscles also withdraws the major parts of their receptive fields when the foot is off the ground. The locations of the nocireceptive fields were independent of the position of the hindlimb. These characteristics of the nociceptive withdrawal reflexes are the basis for their "local sign" (Sherrington 1906). 5. The threshold and the time course of reflex activation were different in different muscles. However, muscles with a similar action; the plantar flexors of the digits, the pronators of the paw, the dorsiflexors of the digits, the flexors of the knee and the adductors, respectively, had similar thresholds and time courses. Furthermore, the threshold and latency of activation of each muscle increased towards the border of its nocireceptive field, reflecting a decreasing sensitivity. These findings explain the progressive recruitment of muscles during increasing strength of noxious stimulation, termed "irradiation" (Sherrington 1906).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

A model for nonexercising hindlimb muscles in exercising animals.

Nonexercising muscles appear to be metabolically active during exercise. Animal models for this purpose have not been established. However, we have been able to teach animals to run on their forelimbs while their hindlimbs are suspended above the treadmill with no visible limb movement. To document that indeed this mode of exercise does not provoke additional muscle activity, we have compared the levels of neural activation of the soleus and plantaris muscles using a computer analysis of the electromyographic interference pattern, recorded from bipolar fine wire electrodes implanted across each muscle. Via computer analyses of the electromyographic interference patterns the frequencies and amplitudes of motor unit action potentials were obtained. The data were sampled during 20 s of every minute of observation. Comparisons were made in four conditions: (i) resting on the treadmill while bearing weight on the hindlimbs (normal rest), (ii) running on the treadmill (15 m/min, 8% grade) on all four limbs (normal exercise), (iii) resting while the hindlimbs were suspended in a harness above the treadmill (suspended rest), and (iv) exercising with the forelimbs (15 m/min, 8% grade) while the hindlimbs were suspended above the treadmill (suspended exercise). All four experimental conditions were carried out for 90 min each and were performed by each animal. The results clearly show that muscle activities (frequencies and amplitudes), when the hindlimbs are suspended above the treadmill, at rest or during exercise, are lower than the activities in these same muscles when the animals are at rest, supporting only their body weight. Activities in the same muscles during exercise were from 300 to 2000% greater than during hindlimb suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine.

Nitric oxide (NO) or related nitroso compounds are an endothelium-derived relaxing factor (EDRF), originating from metabolism of L-arginine, L-Arginine analogues with chemically altered guanidino moity are potent and specific inhibitors of EDRF(NO) release. We evaluated effects of two L-arginine analogues, NG-monomethyl-L-arginine (L-NMMA, 100 microM) and N omega-nitro-L-arginine (L-NARG, 30 microM), on acetylcholine-, substance P-, and nitroglycerin-induced relaxation in the blood-perfused rabbit hindlimb in vivo and femoral arteries in vitro. L-NMMA and L-NARG selectively inhibited the vasodilator response to acetylcholine in rabbit femoral arteries in vitro, whereas endothelium-independent response to nitroprusside increased. L-NMMA (1.6 mg/min ia) in the blood-perfused rabbit hindlimb in vivo increased vascular resistance in the hindlimb by 23 +/- 3% (means +/- SE; n = 10) but did not inhibit the vasodilator responses to acetylcholine or substance P. L-NARG (10 mg/kg iv) increased systemic blood pressure by 26 +/- 3% (n = 7) and vascular hindlimb resistance by 22 +/- 9% (n = 8), and blood flow to hindlimb musculature, measured with microspheres, decreased by 46 +/- 5% (n = 6). Pretreatment with L-NARG, however, did not impair vasodilator responses to acetylcholine and substance P. These findings are consistent with the view that basal tone in resistance vessels in the rabbit hindlimb may be mediated by nitroso compounds, whereas agonist-stimulated vasodilation may be mediated by other mechanisms that do not involve the NO-synthesizing enzyme.

Acetylcholine

Effect of changing metabolic rate on local blood flow control in the canine hindlimb.

This study examined the effect of changing hindlimb metabolic rate on hindlimb blood flow control in anesthetized dogs. The hyperemias induced by graded levels of arterial hypoxia and the degree of steady state autoregulation evoked by changes in blood pressure were measured. Metabolic rate was increased above the resting value by direct electrical stimulation of hindlimb muscles at rates from 0.5 to 1.5 pulses/second, and in three dogs was reduced by cooling. In response to 6 minutes of arterial hypoxia, hindlimb blood flow steadily increased. At rest, and at each level of muscle stimulation, the steepness of the response increased as arterial oxygen saturation (SAO2) decreased. At all levels of SAO2, the response was steeper at increasing stimulation rates. For SAO2 greater than 50%, the relationship between the percentage increase in blood flow from control and SAO2, however, was unaffected by the degree of muscle activity, suggesting that during mild to moderate hypoxia the dynamics of the response were similar whether the muscles were at rest or exercising. The responses to severe hypoxia (SAO2 less than 50%) during stimulation were significantly enhanced compared with those at rest. Autoregulation of blood flow was measured in the steady state by comparing the relative change in blood flow from control with the relative change in blood pressure that produced it. Steady state autoregulation was weak at rest, but improved markedly with increasing muscle stimulation. Conversely, cooling the hindlimb depressed the resting steady state autoregulation. A close correlation was found between the degree of autoregulation and the hindlimb metabolic rate. The results suggest that tissue metabolic rate determines the precision of local blood flow control.

Animals

Contribution of the hindlimb vasculature to systemic resistance responses to carotid sinus pressure changes in the rabbit.

The effects on the vascular resistance of the skinned hindlimb of changes in pressure within the vascularly isolated carotid sinus have been compared with those on systemic vascular resistance in the same rabbits. With the hindlimb perfused at arterial pressure a reduction of sinus pressure from 200 mm Hg to 40 mm Hg increased hindlimb vascular resistance by only 50% compared with an increase of 100% in systemic vascular resistance. Although cardiac output was unaltered, blood flow to the hindlimb increased by 24%. However, flow to the contralateral hindlimb, which had been sympathectomized, rose by 400% and its resistance was halved. These responses to a reduction in sinus pressure show that in the absence of sympathetic tone the hindlimb has a compliant vascular bed and indicate that even though the changes in vascular resistance of the innervated limb were much less than the average systemic resistance change, there must, nevertheless, have been a substantial increase in sympathetic drive to the limb.

Animals

Disynaptic tectal and pyramidal excitation of hindlimb motoneurons mediated by pontine reticulospinal neurons in the cat.

1. The pathway mediating disynaptic tectal and pyramidal excitation of hindlimb motoneurons was analyzed in cats anesthetized with alpha-chloralose or pentobarbital. Stimulation of the contralateral tectofugal fibers induced EPSPs in flexor and extensor hindlimb motoneurons (118/171). EPSP latencies, measured from the monosynaptically evoked descending volley, were 0.8 ms or less in 34 of the 118 motoneurons, suggesting disynaptic linkage from the tectum. The latencies tended to be shorter in motoneurons innervating proximal muscles than in those innervating distal muscles. 2. Stimulation of the cerebral peduncle induced EPSPs only in a small proportion of motoneurons (7/32). But the peduncular stimulation exhibited a marked facilitatory effect on the tectal EPSPs in most of the tested motoneurons (23/27), showing convergence of tectal and peduncular inputs onto relay cells. 3. In animals whose pyramid was transected, the tectal EPSPs were still facilitated by peduncular stimulation in 45 of 48 tested motoneurons. The time course of facilitation indicated convergence of tectofugal and corticofugal fibers onto brainstem relay neurons. 4. Projection of single neurons in the nucleus reticularis pontis caudalis (NRPC) to the gray matter of the hindlimb segments was examined by mapping thresholds of antidromic activation. Twelve of 13 tested neurons were excited by contralateral tectal stimulation at short latencies, probably monosynaptically. Four of them were found to project to lamina IX. Two of the 3 tested neurons projecting to lamina IX were found to receive excitatory input from the cerebral peduncle. 5. Stimulation of NRPC induced monosynaptic EPSPs in hindlimb motoneurons. In 19 motoneurons, the NRPC-induced monosynaptic EPSPs were facilitated by a conditioning tectal shock. This indicated that the tectal stimulus lowered thresholds of direct activation of cell bodies of premotor NRPC neurons. The time course of the facilitation indicated that the NRPC neurons received monosynaptic tectal excitation. The results provide strong evidence that NRPC neurons are involved in mediating disynaptic tectal excitation of hindlimb motoneurons.

Action Potentials

The reflex effect of changes in renal perfusion on hindlimb vascular resistance in anaesthetized rabbits.

This study was designed to characterise the response of the hindlimb vasculature to reduced renal perfusion in the anaesthetized rabbit and to elucidate whether the stimulus was dependent upon reduced renal perfusion pressure (RPP) or blood flow (RBF). Acute decreases in renal perfusion resulted in rapid and reversible increases in femoral perfusion (FPP). This vascular response was completely abolished following renal denervation indicating that the afferent components of the reflex is neurally mediated. Acute hindlimb responses to changes in renal perfusion pressure were present whether the limb was perfused with homologous blood or cross-perfused with blood from a donor rabbit, demonstrating that the efferent component of the response is also neurally mediated. There was a 28-s latency for initiation of the hindlimb vasoconstriction, which is consistent with recent evidence for renal autocoid stimulation of the afferent renal nerve receptors. Decreasing RPP indirectly, by altering flow, resulted in a hindlimb vasoconstriction below approximately 55 mm Hg (7.3 kPa) RPP or 15 ml/min RBF. However, decreasing RPP by directly reducing pressure in graded steps resulted in increases in FPP, which reflected the changes in renal flow; thus during the autoregulatory phase, where flow did not change as pressure fell, FPP also remained stable. The results of these protocols suggest that a neurally mediated hindlimb vascular reflex is stimulated by decreased renal flow rather than pressure.

Anesthesia