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Systemic arterial baroreceptors in ducks and the consequences of their denervation on some cardiovascular responses to diving.

1. In the duck systemic arterial baroreceptors which cause bradycardia in response to induced hypertension are located in the walls of the ascending aorta, innervated by the depressor nerves.2. The location of the baroreceptors was confirmed both histologically and by recording activity from the depressor nerve. Stimulation of the central cut end of a depressor nerve caused transient bradycardia and a fall in blood pressure which was maintained throughout the period of stimulation.3. Cardiovascular adjustments to submergence of 2 min duration were monitored in intact, sham-operated and denervated ducks. The sham-operated and denervated ducks were used in the experiments some 20-50 days post-operation. The denervations were checked at post-mortem.4. In the first series of experiments on young ducks mean arterial pressure during a 2 min dive fell by 30% in intact, 17.5% in sham-operated, and 48% in denervated ducks. In all ducks heart rate was reduced by 84-85%.5. In a second series of experiments on older ducks sciatic artery blood flow was also recorded and mean arterial blood pressure fell by 9.2% in intact and by 53% in denervated animals, although there were no significant differences in heart rate during the 2 min dives. In normal animals sciatic vascular resistance increased after 2 min submergence by 7.86 +/- 1.7 times, whereas in denervated ducks it increased by only 2.32 +/- 0.5 times.6. The role of systemic arterial baroreceptors in generation of the cardiovascular responses to submergence in ducks is discussed in terms of the input supplied by the baroreceptors to the central nervous system.

Action Potentials↗

Two factors responsible for the development of denervation hypersensitivity.

1. Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive. The period of greatest increase in sensitivity in rat soleus muscles following section of the sciatic nerve in the thigh is between 48 and 72 hr post-operatively.2. Direct electrical stimulation was found to prevent the onset of the development of denervation hypersensitivity during the first 2-3 days after nerve section. Thereafter, electrical stimulation only reduced the sensitivity of denervated muscles to acetylcholine (ACh).3. The period of greatest increase in sensitivity follows loss of transmission and degeneration of the nerve terminals. Once this degeneration is under way, electrical stimulation is no longer as effective in preventing the development of denervation hypersensitivity.4. Hypersensitivity is also seen in muscles on which a small piece of thread or degenerating nerve has been placed. Hypersensitivity following these procedures declines within a few days, unlike denervation hypersensitivity which persists until innervation is restored.5. The present results suggest that activity alone cannot prevent the development of hypersensitivity in the presence of degenerating nerve fibres, or muscle damage. Activity does however counteract increased sensitivity. It is suggested that two factors interact to produce denervation hypersensitivity; the presence of degenerating nerve tissue and concomitant cellular changes bring about changes in the muscle fibre membrane causing it to become hypersensitive; and the loss of muscle activity, resulting in the persistence of hypersensitivity until innervation is restored.

Acetylcholine↗

Effect of denervation on the adaptation of sarcomere number and muscle extensibility to the functional length of the muscle.

1. The effects of denervation on the response of the cat soleus muscle to immobilization at different lengths by plaster casts has been investigated for a period of 4 weeks.2. The passive length-tension properties of the denervated immobilized muscles were not significantly different from those of non-denervated muscles. Muscles immobilized in the shortened position showed a marked decrease in extensibility whether they were denervated or not. In all the other cases the length-tension curves were not significantly differetn from those of normal muscles.3. The denervated soleus muscle immobilized in the lengthened position was found to produce 25% more sarcomeres in series, whilst those immobilized in the shortened position lost 35%. This adaptation was essentially the same as in muscles that had been immobilized but not denervated.4. Denervation was found to have no effect on the recovery of muscles that had been subjected to 4 weeks immobilization in the shortened position. In these muscles the sarcomere increased back to the normal level within 4 weeks after removal of the plaster cast.5. The adjustment of sarcomere number to the functional length of the muscles does not therefore seem to be directly under neuronal control. It appears to be a myogenic response to the amount of passive tension the muscle is subjected to.

Animals↗

Neurotrophic regulation of dynamic properties of skeletal muscle: effects of botulinum toxin and denervation.

In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of dynamic properties of muscle, the effects of botulinum toxin treatment were compared with those of denervation. The extensor digitorum longus (EDL) and soleus muscles of rats were either denervated or injected with botulinum toxin. At times up to 25 days the isometric properties of these muscles were determined. 2. Both botulinum treatment and denervation produced progressive slowing of the time to peak of the twitch (TPT) and half-relaxation time of the twitch (1/2 RT), which was more pronounced in the EDL than in the soleus. 3. Both treatments produced slowing of the relaxation curve following tetanic contraction, more marked in the EDL than in the soleus muscle. This indicates a slowing of relaxation, and suggests a prolongation of the active state of the muscle. 4. The maximum rate of rise of the tetanus did not change significantly in the EDL and soleus muscles after botulinum treatment or denervation. This suggests that there is no major change in the speed of contraction under conditions of botulinum treatment or denervation. 5. The changes produced by botulinum treatment and denervation were virtually identical in all parameters tested. This is interpreted meaning that cholinergic transmission (including muscle usage), or some other factor closely related to cholinergic transmission, accounts for the motor nerve's trophic influence in maintaining these dynamic properties of skeletal muscles.

Acetylcholine↗

Respiratory and cardiovascular interactions in ducks: the effect of lung denervation on the initation of and recovery from some cardiovascular responses to submergence.

Lung denervation in ducks, by sectioning all vagal branches to one lung following mid-cervical vagotomy on the other side, resulted in immediate bradycardia and fall in breathing frequency. Some 3-5 weeks after lung denervation breathing frequency was within the normal range but the lung inflation reflex, present in unilaterally vagotomized sham-operated ducks, was abolished. During 2 min dives there were no significant differences between sham-operated and denervated ducks in heart rate, arterial blood pressure, blood gas tensions and pH(a). However, during recovery from diving heart rate increased more slowly in denervates and breathing rate was significantly below that attained by shams, although tidal volume rose to a maximum increase of 139% to a maximum of 225% of the pre-dive value in denervates in contrast to a maximum increase of 139% of pre-dive in sham-operated ducks. Both sham-operated and denervated ducks exhibited a significant fall in diastolic blood pressure 60 sec after emergence...

Action Potentials↗

Reaction of intact spinal motoneurones to partial denervation of the muscle.

1. The properties of soleus motoneurones of the cat were examined with intracellular electrodes about 3 weeks after partial denervation of the soleus muscle. Soleus motoneurones whose axons had been left intact were distinguished from those whose axons had been sectioned by the presence or absence of muscle contraction in response to intracellular stimulation of each motoneurone. 2. The average twitch tension of motor units evoked by intracellular stimulation of intact soleus motoneurones after partial denervation of the muscle was not significantly different from that observed in control, unoperated cats. Therefore, it was assumed that the majority of intact motoneurones had not been subject to injuries in their axons upon partial denervation. 3. Soleus motoneurones whose axons had been sectioned showed a significant increase in overshoot of action potentials and a significant decrease in resting membrane potential, in axonal conduction velocity and in the duration of after-hyperpolarization. 4. Soleus motoneurones whose axons had been left intact also showed a significantly shorter after-hyperpolarization than that seen in control, unoperated cats. Other electrophysiological properties of the intact soleus motoneurones were indistinguishable from those observed in unoperated animals. 5. The decrease of the duration of after-hyperpolarization in intact soleus motoneurones was greater in highly denervated preparations than in moderately denervated preparations. 6. The decrease of the duration of after-hyperpolarization in intact soleus motoneurones was associated with a decrease in contraction times of the innervated muscle fibres, the former preceding the latter by one to two weeks. 7. It is concluded that motoneurone properties can be modified without injury to their axons and that alterations in the properties of intact motoneurones depend upon the degree of partial denervation of the muscle. The possible signal for alterations of motoneurone properties is discussed. 8. It is also concluded that the contractile properties of muscle fibres can be modified without cross-union of the nerves. It is suggested that the contractile properties of muscle fibres may be linked to the duration of after-hyperpolarization or to some mechanism related to this factor in the innervating motoneurones.

Action Potentials↗

Normal distribution and denervation changes of neurotransmitter related enzymes in cholinergic neurones.

1. The activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were assayed in adult pigeon ciliary ganglia, in the post-synaptic ciliary and choroid nerves, and in ciliary nerve iris terminals isolated from control birds and from animals from which the oculomotor nerve was previously transected. Enzyme activity levels were also measured in the iris terminals after surgical section of the ciliary nerves. From differences in enzyme activity between control and 3-day denervated tissues, the localization of CAT and AChE in pre- and post-synaptic elements of the ganglia and at the iris neuromuscular junctions was estimated. The fate of the preganglionic nerve terminals after denervation was investigated by electron microscopic examination of ganglia after surgical section of the oculomotor nerve.2. The CAT activity in the ganglion was distributed as follows: 60% in presynaptic elements, 31% in cell somas, and 9% in intraganglionic post-synaptic axons; in the iris junctions, 98% of the activity was present in the ciliary nerve terminals. For AChE: 20% was present in the preganglionic terminals, 69% in ganglion cell somas and the remaining 11% in post-ganglionic axons; at the neuromuscular iris junctions, 20% was found in the ciliary nerve terminals and 80% in the iris striated muscle.3. The first changes in the fine structure of the nerve terminals were observed 14 hr after surgery, and by 24 hr marked alteration of the synaptic structure were clearly recognized. No preganglionic endings were found in 3 day-old denervated ganglia.4. There was a positive correlation between CAT activity in the control iris nerve terminals and in ganglia. After denervation, when the activity of the enzyme decreased in ganglion cell somas, there was a corresponding decrease in the post-synaptic nerves. These two findings suggest that CAT slow axoplasmic transport is related to its perikarial concentration.5. There was a 60% reduction of CAT activity in the post-synaptic elements, assayed in the 10-day denervated ganglia, which was accompanied by a 30% decrease in activity in the iris nerve terminals. Similarly, post-synaptic AChE decreased approximately 30% in the ganglion and approximately 30% in the iris 10 days after section of the oculomotor nerve. At the same time, CAT activity also decreased in the nerve trunks, 70% at the ciliary nerve and 40% at the choroid; for AChE there were smaller changes.6. In contrast to CAT and AChE, there were no differences in ganglionic protein content, or lactate dehydrogenase (LDH), co-enzyme A (CoA) and monoamine oxidase (MAO) levels between short-term (3 days) and long-term (10 days) denervated ganglia.7. The later decrease of CAT and AChE activity in the cell somas, axons and nerve terminals after long-term preganglionic transection suggests that the activity of these enzymes is regulated across the synapses. It is postulated that the AChE regulation is part of a general ;trophic interaction' between neurones, but that the trans-synaptic modulation of CAT is specific for cholinergic cells.

Acetylcholinesterase↗

Neuromuscular junctions and alpha-bungarotoxin-binding sites in denervated and contralateral cat skeletal muscles.

1. The distributions of cholinesterase (ChE) activity and acetylcholine (ACh) receptors were studied in normal and denervated cat hind-limb fast-twitch skeletal muscles and in muscles contralateral to denervated muscles. 2. On normal muscle fibres almost all receptors were confined to the immediately post-junctional membrane, although a perijunctional gradient of increased ACh receptor density was found on both fast- and slow-twitch fibres. After denervation, the extrajunctional ACh receptor density increased greatly and remained high for at least 10 months. Ectopic regions staining for ChE activity and having a high density of ACh receptors appeared in denervated muscle. The number of junctional ACh receptors decreased slowly after denervation, with a half-time of about 140 days. 3. Fast-twitch muscles contralateral to denervated muscles also showed changes, including an increase in junctional size and a small but significant increase in extra-junctional ACh receptor density.

Acetylcholine↗

The effects of electrical stimulation on sprouting after partial denervation of guinea-pig sympathetic ganglion cells.

1. The effects of electrical stimulation of presynaptic and post-synaptic cells on sprouting after partial denervation were examined in the guinea-pig superior cervical ganglion with intracellular recording. The partial denervation reduced the mean number of preganglionic axons innervating each ganglion cell from about eleven to about two (Maehlen & Njå, 1981). 2. One week after partial denervation alone, the number of residual preganglionic axons innervating each superior cervical ganglion cell was increased by about 30%. This means that the number of ganglion cells contacted by each residual preganglionic axon was increased by the same amount, which represents an early stage of sprouting. 3. Preganglionic stimulation for 1 hr immediately after the partial denervation (with 100 pulses at 20 Hz every 25 sec) increased the rate of sprouting. Thus 1 week after partial denervation and preganglionic stimulation the number of residual preganglionic axons innervating each ganglion cell was increased by about 70%. Preganglionic stimulation had no similar effect on the innervation of normal ganglia. 4. The acceleration of sprouting caused by preganglionic stimulation was abolished by blocking ganglionic transmission with hexamethonium (30--60 mg kg-1 hr-1 I.V.) during the stimulation. 5. Furthermore, the rate of sprouting of residual preganglionic axons was increased by electrical stimulation of the ganglion cells alone. 6. These results show that after partial denervation of the superior cervical ganglion, a period of impulse activity in ganglion cells enhances their subsequent ability to receive innervation from sprouts arising from residual preganglionic axons.

Animals↗

The synthesis and release of acetylcholine in normal and denervated rat diaphragms during incubation in vitro.

1. Normal and denervated rat diaphragms and neural (central) and aneural (peripheral) parts of normal diaphragms were incubated under several different conditions likely to affect the metabolism of acetylcholine (ACh), with the aim of discovering specific features of the control of neural and aneural ACh in the muscle. The concentrations of ACh in the tissue and the medium were measured at the end of the incubations using a radioenzymatic assay, and the amount of ACh synthesized during the incubations was calculated by subtracting the initial amount of ACh present in the tissue from that found in the tissue plus the medium at the end of the incubations.2. Confirming earlier results obtained with bioassays, it was found that, in a medium with 5 mM-K(+) and 2.5 mM-Ca(2+), denervated diaphragms released ACh into the medium at a rate equal to 47% of that observed in normal diaphragms; the amount of ACh released from aneural parts of normal diaphragms was 51% of that released from their neural parts. The release from normal diaphragms was increased (83%) in a Ca(2+)-dependent manner by raising the concentration of K(+) to 30 mM. In the denervated diaphragms, 30 mM-K(+) brought about a Ca(2+)-independent increase (67%) in the rate of ACh release. The elevation of K(+) was without effect on the release of ACh from aneural parts of normal diaphragms.3. The results indicate that a Ca(2+)-dependent mechanism of ACh release, known to function in the nerve terminals, is not likely to participate in the efflux of ACh from the muscle fibres. The K(+)-induced but Ca(2+)-independent enhancement of ACh release from the denervated diaphragms probably occurs by diffusion of ACh along the altered electrochemical gradient. It is suggested that the surface membranes of the muscle fibres become more permeable to ACh after denervation.4. During incubations with 30 mM-K(+) and 10 muM-hemicholinium-3 (HC-3), an inhibitor of the carrier-mediated transport of choline, the rates of ACh release and synthesis in normal diaphragms were diminished to the levels found in the denervated diaphragms, in which the concentration, release and synthesis of ACh were not affected by HC-3. The synthesis of aneural ACh thus appears to be independent of the carrier-mediated supply of choline across cell membranes.5. The release of ACh from normal diaphragms incubated with 5 mM-K(+) was increased in the presence of 100 muM-ouabain, whereas the release from denervated diaphragms was not affected. This finding suggests that the mechanism of ACh release that is activated by ouabain in the nerve cells involves, in addition to the inhibition of Na(+)-K(+)-ATPase, some other steps which are not operative in the muscle fibres.6. The results corroborate earlier evidence indicating that aneural ACh is produced, stored and released in the diaphragms. They fit the view that the aneural ACh is located in the cytoplasm of the muscle fibres and that it leaves the muscle fibres by molecular ;leakage' rather than by a specialized release mechanism. The efflux of ACh from the muscle fibres is likely to constitute about 50% of the total resting efflux (release) of ACh from normal diaphragms.

Acetylcholine↗

Sino-aortic denervation in the monkey.

The aortic arch and carotid sinuses were denervated in eleven monkeys. The monkeys were subjected to four sequential surgeries which involved: (1) implantation of an aortic and left atrial catheter; (2) stripping of the adventitia from the aortic arch; (3) stripping the left carotid sinus and associated vessels; and (4) stripping the right carotid sinus and associated vessels. Blood pressure and pulse rate were recorded 6 days after each surgical procedure. Records were taken over a 6 h period while the monkeys were in their home cages. Baroreceptor denervation was confirmed by: (1) absence of heart rate response to blood pressure changes and (2) an increase in the variability of blood pressure. Veratridine given into the left atrium caused a Bezold-Jarisch reflex both before and after denervation verifying the integrity of the afferent and efferent vagus. Denervation of the baroreceptors resulted in a significant increase in blood pressure when measured from monkeys who were restrained in chairs in the laboratory; however, blood pressure was not significantly elevated in the baroreceptor denervated monkeys while they were tethered in their home cages. It is concluded that denervation of the sino-aortic baroreceptor does not result in a significant increase in systemic blood pressure.

Animals↗

Induction of action potentials by denervation of tonic fibres in rat extraocular muscles.

The effects of denervation by nerve section on the electrical properties of tonic and twitch fibres of rat extraocular muscles were examined. Normally innervated tonic fibres lack action potentials. Upon direct stimulation they generate graded, voltage-dependent responses or slow peak potentials (s.p.p.s). However, one week after denervation the s.p.p.s are transformed into action potentials which are slower and broader than those of twitch fibres. The action potentials are Na dependent and partially resistant to blockade with 10(-5) M-tetrodotoxin and 10(-6) M-saxitoxin. Changing the holding potential of the fibres from -80 mV to more negative levels increases the maximal rate of rise of the action potential. This effect is not observed on the s.p.p.s of normally innervated fibres. Following denervation the resting potential of tonic and twitch fibres becomes about 10-15 mV less negative. In denervated muscles stimulation with pulses of hyperpolarizing current evokes graded responses in tonic fibres and action potentials in twitch fibres. In normally innervated muscles, these anodal break responses are never observed in tonic fibres and are very rare in twitch fibres. By two weeks after nerve section, reinnervation is present. The action potentials of tonic fibres are still present but stronger stimulation is needed to evoke anodal break responses. By three weeks, direct stimulation of tonic fibres evokes normal s.p.p.s in about 25% of the studied fibres and action potentials in the rest. By four weeks, most tonic fibres have lost the action potential but small anodal break responses can be evoked in most. It is suggested that following denervation a new population of Na channels appears in tonic fibres. The properties of these channels are different from those of the channels normally present in innervated tonic fibres but they are in some ways similar to those of the channels which appear in twitch fibres following denervation.

Action Potentials↗

Temporary loss of activity prevents the increase of motor unit size in partially denervated rat soleus muscles.

1. The effects of temporary short-term paralysis on changes of motor unit size and amount of sprouting after partial denervation of the rat soleus were studied. 2. Two to ten months after section of the L5 ventral ramus combined with subsequent treatment with alpha-bungarotoxin (BTX) the tension developed by the operated muscle was 39 +/- 8% (S.E.M., n = 8) of control unoperated soleus muscles. This is much less than the tension produced by partially denervated, NaCl-treated or untreated muscles which was 66 +/- 9% (S.E.M., n = 5) and 66 +/- 12% (S.E.M., n = 5) respectively. The smaller tension developed by the BTX-treated muscles was due to the relatively small size of their motor units. 3. The mean increase of tension output of individual motor units after partial denervation and treatment with NaCl when compared with controls was 194 +/- 15% (S.E.M., n = 4) while in the paralysed muscle this value was only 118 +/- 15% (S.E.M., n = 8). This reduced expansion of motor unit size in the BTX-treated soleus was not caused by a decrease of the size of the muscle fibres. Thus a brief temporary paralysis prevents the expansion of motor unit territory that normally occurs in partially denervated muscles. 4. Examination of the innervation pattern and incidence of sprouting revealed that in partially denervated NaCl-treated muscles 24 +/- 4% (S.E.M., n = 4) of endplates was contacted by either terminal or collateral sprouts, whereas in the BTX-treated muscles only 5 +/- 2% (S.E.M., n = 3) of endplates had been contacted by sprouts. Treatment with BTX alone, without partial denervation, did not affect the tension output of the muscles, but caused 8 +/- 5% (S.E.M., n = 3) of the endplates to become innervated by collateral sprouts, as compared to only 3 +/- 2% (S.E.M., n = 3) in controls.

Animals↗

Denervation of carotid baro- and chemoreceptors in humans.

Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.

Animals↗

Comparison of the intermediary metabolism of fatty acids in denervated and dystrophic murine skeletal muscle.

Certain aspects of lipid metabolism have been examined in denervated muscle from normal mice and in dystrophic muscle from mice of the Bar Harbor strain 129. A number of parameters show no change or similar changes. For example, the utilization of palmitate-[1-14C] and palmitylcarnitine by mitochondria from denervated and dystrophic hind leg skeletal muscle showed parallel decreased in the oxidation of palmitate (30-42%) and palmitylcarnite (37-66%). A comparable study with acetylcarnitine showed a striking difference with no change evident in mitochondria from denervated muscle and 80-85% decrease in dystrophic muscle. The study of succinate dehydrogenase and the enzymes of beta-oxidation in the above mitochondrial preparation showed similar findings except for acyl CoA dehydrogenase activity (an enzyme with a regulatory role in beta-oxidation) which was significantly diminished (29%) in denervated muscle, whereas no change was observed in dystrophic muscle. The findings show a close parallel in a number of parameters but distinct differences were observed in denervated as compared with dystrophic muscle. It is unlikely that the muscular disorder in murine muscular dystrophy can be explained solely on the basis of denervation or the loss of a neural trophic factor.

Acyl-CoA Dehydrogenases↗

Selective loss of uncoupling protein from mitochondria of surgically denervated brown adipose tissue of cold-acclimated mice.

The effects of unilateral surgical denervation on brown adipose tissue (BAT) composition were evaluated to assess the importance of the sympathetic innervation in the maintenance of a high concentration of the uncoupling protein thermogenin in cold-acclimated (CA) mice and to assess whether suppression of neural activity could account for BAT atrophy observed during fasting or when CA mice are returned to a thermoneutral environment (33 degrees C). Denervation-induced BAT atrophy was characterized by protein and thermogenin losses in absence of changes in the tissue cellularity (DNA content). There was a marked reduction in the concentration of thermogenin in mitochondria isolated from denervated BAT, but the concentration of the adenine nucleotide translocator was unchanged. Fasting or exposure of CA mice to 33 degrees C induced a rapid and extensive loss of tissue protein from both innervated and denervated BAT. In CA mice exposed to 33 degrees C, there was also reduction in tissue cellularity and loss of thermogenin from BAT mitochondria. Since surgical denervation suppressed BAT hyperplasia and the increase in the mitochondrial concentration of thermogenin observed during cold exposure, these results indicate that an intact innervation is required for both synthesis and maintenance of a high mitochondrial content of thermogenin in CA mice. In addition, the lesser changes in tissue composition caused by denervation compared with those caused by fasting or exposure of CA mice to 33 degrees C question the importance of the suppression of neural activity as the exclusive cause of rapid BAT atrophy in mice.

Acclimatization↗

Effect of renal denervation, furosemide, and acute saline loading on postobstructive diuresis in the rat.

The effect of acute or chronic renal denervation, furosemide, or acute saline loading on the postobstructive diuresis (POD) which occurs after relief of 24-h bilateral ureteral obstruction (BUO) was studied in anaesthetized rats. Acute renal denervation during POD 1--2 h after relief of BUO had no effect on glomerular filtration rate of sodium, potassium, water, or solute excretion, in contrast with its natriuretic and diuretic effect in sham-operated rats. Intravenous furosemide or acute saline loading caused a further marked increase in sodium and water excretion during POD, demonstrating the ability of the kidney undergoing POD to respond to other types of natriuretic stimuli. Chronic renal denervation prior to BUO had no effect on subsequent POD. The lack of response of the BUO kidney undergoing POD to acute denervation contrasts with the changes in renal function following denervation of the unilateral postobstructive kidney. The results indicate that the kidney undergoing POD after relief of BUO may be functionally denervated and suggest that inhibition of renal nerve activity could contribute to the pathophysiology of POD.

Animals↗

Changes in isometric contractile properties of extensor digitorum longus and soleus muscles of C57BL/6J mice following denervation.

In this study, conducted on mice of the C57BL/6J+/+ strain, we investigated the differential effects of denervation on the isometric contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles. The contractile properties were studied at 1, 28, 84, and 210 days following unilateral section of the sciatic nerve at 12 weeks of age. When isometric tetanus tension was expressed relative to wet weight, the denervated SOL showed an earlier and more pronounced loss in tension generating capacity than the EDL. Both the denervated SOL and EDL showed potentiation of the twitch tension at 28 days postdenervation. The time to peak twitch tension (TTP) and the time to half-relaxation (1/2RT) were prolonged by 28 days postdenervation in both muscles. This trend continued to the oldest age-groups studied in the EDL, but reached an apparent plateau in the SOL at 84 days postdenervation. In response to fatigue, the denervated SOL showed a marked decrease in resistance to fatigue at 1 day but a relatively normal response thereafter, whereas the denervated EDL showed an increase in resistance to fatigue at and beyond the 28-day period. In spite of the fact that the total contraction time of both muscles increased following denervation, the predominantly oxidative SOL remained a slower contracting muscle than the more glycolytic EDL.

Animals↗