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Attenuation of hypothalamo-sympathetic hyperactivity by renal denervation in experimental hypertensive rats.

To clarify the effect of renal nerves on hypothalamic cardiovascular regulation in hypertension, posterior hypothalamus was electrically stimulated in renal denervated SHR (RD-SHR) and DOCA hypertensive (RD-DOCA) rats during recording blood pressure and sympathetic nerve activity. In urethane anesthetized SHR, mean blood pressure was not different between RD- and sham-operated SHR 48 hours after denervation, but two weeks later, blood pressure was lower in RD-SHR. Pressor and sympathetic nerve responses to hypothalamic stimulation were partly attenuated 48 hours after denervation, but two weeks later, attenuation was strong. The development of hypertension was abolished during two weeks observation in RD-SHR. In DOCA hypertensive rats, the development of hypertension was significantly inhibited by renal denervation. Pressor and sympathetic nerve responses to hypothalamic stimulation were significantly diminished in RD-DOCA rats. Water intake and urine volume was identical in both groups. These results suggest that renal denervation inhibited the development of hypertension accompanied with the inhibition of hypothalamo-sympathetic nerve system, furthermore, it is indicated that hypothalamic cardiovascular regulation controlled by afferent renal nerve could contribute to the development of hypertension in SHR and DOCA hypertensive rats.

Animals↗

Unlike effects of denervation on the rate of entry of inorganic phosphate into rat slow and fast muscles.

The increased inorganic phosphate flow, characteristic of denervated gastrocnemius muscle is shown to be present in additional denervated fast muscles, i.e. the plantaris, tibialis anterior and extensor digitorum longus muscles. The response of the soleus, a slow muscle, to denervation is biphasic. After an initial decrease of the phosphate flow at the end of the first postoperative day, there is a secondary rise which has the same general characteristics as the rise observed in fast muscles i.e. an exponential or hyperbolic increase to an asymptotic value reached after thirty days. The denervated fast and slow muscles are not converging to an intermediate metabolic pattern. The changes in phosphate flow induced by denervation are reversible in the soleus as well as in the gastrocnemius muscles.

Animals↗

Effect of acute and chronic cardiac denervation on osmotic release of vasotocin in chickens.

Hypo- and hyperosmotic NaCl were infused intravenously to examine osmotic release of arginine vasotocin (AVT) in anesthetized, acutely cardiac-denervated chickens and in conscious, chronically denervated birds. Mean arterial blood pressure was consistently higher in denervated compared to sham-operated chickens but heart rates were similar in experimental and control groups. Plasma AVT concentrations (pAVT) were significantly higher than controls in acutely, but not chronically, denervated chickens. The slope of the regression line relating pAVT to plasma sodium concentration was higher in denervated birds indicating that removal of cardiac receptor activity increases the osmotic sensitivity of the AVT system. The results suggest that cardiac end-net receptor activity may participate in the regulation of blood pressure and can modulate the release of antidiuretic hormone in the chicken.

Animals↗

The effect of denervation and dystrophy on the adaptation of sarcomere number to the functional length of the muscle in young and adult mice.

In young animals the elongation of the limb bones increases the functional lengths of the muscles. In adult animals the functional length of a muscle can be increased by immobilizing it in the lengthened position. In both cases the muscle adapts by adding on more sarcomeres in series. The role of the nerve supply in this adaptation has been investigated using denervated muscles and muscles from dystrophic animals where there is thought to be an abnormality of the nerve supply. Postnatal sarcomere addition in denervated muscles falls short of that of controls. Although this might mean that the nerve supply is necessary for normal addition of sarcomeres, it is just as likely that there is a change in gait resulting from denervation, which affects the sarcomere number. Sarcomere number in fully grown mice is not affected by denervation, nor is the ability of the muscle to adapt to immobilization in the lengthened position. This is true for fast-twitch as well as slow-twitch muscles. In dystrophic muscles postnatal sarcomere addition is normal, although the presence of a few short fibres in the muscle may mean that some muscle fibres cannot adapt to an increase in the functional length of the muscle accompanying bone growth. Adult dystrophic muscle is capable of adapting to immobilization in the lengthened position. However, although the total number of additional sarcomeres is the same as in normal immobilized muscle, they are added on at a slower rate. The experiments show that although denervated and dystrophic muscle fibres are in a state of atrophy they are still capable of adding on sarcomeres in series when the functional length of the muscle is increased. It would appear that the mechanism which enables the muscle to respond in this way to an increased functional length does not involve the nerve supply. This work was supported by a grant from the National Fund for Research into Crippling Diseases.

Age Factors↗

[Experimental study on denervated skeletal muscle autotransplantation in the rhesus monkey].

OBJECTIVE: This study was to provide a scientific basis for clinical application of denervated muscle transplantation. METHODS: A rhesus monkey was used in this experiment. The denervated extensor digitorum brevis (EDB) and the extensor hallucis brevis (EHB) of the rhesus monkey were autotransplanted in the sacrospinal muscle, and they were biopsied at intervals and stained with HE, Bielshowsky and enzyme. The specimen were examined with light and electro-microscope. RESULTS: The metabolism of the denervated muscle was lower than the normal. There was muscle regeneration and growing nerve fibers in the graft 12 weeks after transplantation. CONCLUSION: Denervated muscle can regenerate in oxygen-deficient environment. If the denervated muscle is in contact with normal muscle, the nerve of the recipient muscle will grow into the graft.

Animals↗

The expression kinetics of myogenin in facial muscle denervation.

OBJECTIVE: To study the expression kinetics of myogenin in long-term denervated facial muscle and to explore the possibility of gene therapy for facial muscle paralysis with myogenin gene. MATERIALS AND METHODS: In 48 New Zealand rabbits, buccal muscle paralysis of one side was produced by excision of 1 cm segment buccal branch of the facial nerve. The opposite side served as controls. The animals were sacrificed and the buccal muscles of both sides were removed for examination at 1 day, 3 days, 1 week, 2 weeks, 1 month, 2 months, 4 months, and 6 months after the initial operation. The myogenin expression in denervated and innervated buccal muscles was analyzed by Western blot. Satellite cell proliferation was detected with proliferating cell nuclear antigen (PCNA) analysis. Muscle nucleic acid concentration was determined through acridine orange (AO) staining method. RESULTS: Myogenin expression increased to the highest level at 3 days after denervation, thereafter it gradually decreased. The Western blotting signal for myogenin intensified again after 1 month and at 4 months. In contrast, the highest expression of the controls (innervated muscles) were observed at 1 month. These changes in myogenin expression in denervated buccal muscles were consistent with the change in satellite cell proliferation and in muscle nucleic acid concentration. CONCLUSION: Myogenin protein expression in longterm facial muscle denervation is closely associated with satellite cell regeneration. Myogenin may promote satellite cell differentiation, and therefore may improve the treatment of facial paralysis.

Acridine Orange↗

Development of supersensitivity in denervated slow muscle of the frog. Its dependence on the nerve stump length.

Sensitivity to carbachol has been studied in paired normal and denervated gastrocnemius slow muscle fibers of the frog. Dose response curves showed that after 25 days the ED50 was ten times less in denervated muscle than in the normal. The denervated muscle showed a three-fold increase in affinity constant to d-tubocurarine. In studying the development of supersensitivity of paired muscles denervated near or far from the neuromuscular junction it was found that muscles with a long axon stump started to increase sensitivity three days later than muscles with a short stump. We suggested that in slow muscle fibers, denervation supersensitivity is not only due to a spread in cholinergic receptor area but also to a change in the receptor properties. As the onset of the supersensitivity depends on the length of the nerve stump, it is also suggested that it is regulated by presynaptic factors which would be transported along the axon at a rate of a few centimeters per day.

Amputation Stumps↗

Effect of denervation on the phospholipid content in subcellular fractions of tonic and tetanic muscles.

Four weeks after denervation, various changes were observed in the phospholipid composition of the sarcolemmal and sarcoplasmic fractions of skeletal muscles with different functions. Neurotomy also affected the innervated contralateral muscles and produced opposite changes in the phospholipid content of subcellular fractions. The increase in the amount of phospholipids in the sarcolemmal fractions of the denervated muscles was only apparent. The difference between the denervated and contralateral muscles was also due to the decrease of phospholipids in the contralateral muscles. These changes were more pronounced in the tetanic (fast-twitch) than in the tonic (slow-twitch) muscles. In the sarcoplasmic fraction of the denervated tetanic muscle an increase, while in that of the tonic one a slight decrease of phospholipids appeared. In contrast, the phospholipid content in the sarcoplasmic fractions of contralateral muscles did not decrease, while it increased slightly in the tonic muscle. The amount of plasmalogens (fatty aldehyde: lipid phosphorus ratio) decreased only in the subcellular fractions of the denervated muscles while there was no change in those of the contralateral muscles.

Aldehydes↗

[Muscle spindles in denervated and reinnervated m. soleus of the rat. II. Changes in the extra- and intrafusal muscle fibers].

After a transient or permanent unilateral denervation of the soleus muscle of the rat changes were investigated of extra- and intrafusal muscle fibres of the denervated (reinnervated) muscle as well as its contralateral still innervated muscle. Those data which were obtained from normal muscles of uninjured rats served as control. The changes of permanent denervated muscles were clear and statistically significant. The extrafusal muscle fibres show a considerable atrophy. The nuclear-chain fibres exhibit a decrease of their calibres. The extent of this atrophy is not as pronounced as in extrafusal muscle fibres. The nuclear-bag fibres show 12 weeks after denervation a small atrophy (or pseudoatrophy) and 18 weeks after denervation a significant hypertrophy. At the same time the number of nuclear-bag fibres is increasing. Besides the increase in number of intrafusal muscle fibres per muscle spindle, a change is observed of proportion of both intrafusal fibre types in favour of nuclear-bag fibres. The hypertrophy and the increase in number of the nuclear-bag fibres are discussed in connection with their functional properties.

Animals↗

Effect of electrostimulation on denervated muscle.

The influence of electrostimulation on denervated and reinnervated muscle was investigated. First, the left peroneal nerve was severed in rats. Wet weight and muscle fiber diameter of denervated anterior tibial muscle was compared as a percentage of contralateral muscle in stimulated and non-stimulated rats. In a second experiment, four weeks after the peroneal nerve was severed, the tibial nerve was cross-sutured to the distal stump of the peroneal nerve. Electrostimulation was continued in rats that had electrostimulation before nerve-crossing. Recovery of wet weight was assessed at eight weeks and at one year after nerve-crossing. The mean decrease in weight and fiber diameter of the denervated muscle was significantly less in the group that was electrostimulated for eight weeks. Recovery of weight of reinnervated muscle was significantly better in the electrostimulated group. Electrostimulation of denervated muscle retarded denervation atrophy and improved recovery after reinnervation.

Animals↗

[Influence of clenbuterol on the sensory neurotrophic activity of denervated red and white muscles].

OBJECTIVE: To investigate the influence of clenbuterol on the expression of nerve growth factor (NGF) in denervated red and white muscles and the neurotrophic activity of the denervated muscles. METHODS: Sixty-four Wistar rats, weighed 200-250 g, were divided into 8 groups (8 rats per group), including 4 experimental groups and 4 control groups. The denervated model was made in rats by dissection of sciatic nerves. Clenbuterol was given at a dose of 200 microg/kg per day in the experimental group, saline in the control group. The expression of NGF was measured with immunohistochemistry after 1, 3, 7 and 14 days of injury. The culture methods of dorsal root ganglions of the chick embryos were used to measure the neurotrophic activity of extracts of the muscles. RESULTS: Compared with the control groups, the NGF content of gastrocnemius (GAS) increased on the 1st day (P<0.05) and the NGF content of soleus (SOL) increased greatly on the 1st, 3rd and 7th day after injury in the experimental groups (P<0.01). In the experimental groups, the NGF amount of GAS reached the highest value on the 1st day after injury (P<0.01) and then decreased gradually. And the NGF amount of SOL had slight difference between different time. The NGF content of the SOL was higher than that of GAS on the 7th day (P<0.05). The sensory neurotrophic activity of the extracts was similar between SOL and GAS. CONCLUSION: Clenbuterol can change the expression of NGF in denervated muscles, but the change was different in SOL and GAS. The sensory neurotrophic activity of the denervated muscles were determined by all of the neurotrophic factors in them.

Animals↗

[Partial denervation of the wrist by excision of the interosseous nerves from the dorsal approach].

PURPOSE OF THE STUDY: The aim of the study was to optimize, on the basis of an anatomical study, the technique of partial denervation of the wrist in terms of safety for preserving motor innervation of the quadrate pronator muscle, and to include this technique in the range of reconstruction operations for the treatment of degenerative carpal diseases. MATERIAL AND METHODS: The technique of partial denervation of the wrist, using excision of the sensitive branches of the dorsal and volar interosseous nerves, carried out by one-stage surgery from the dorsal approach is presented in a group of 28 patients. The partial denervation was always performed in addition to reconstructive surgery on the proximal carpals and the distal radioulnar joint. On the basis of an anatomical study involving 40 cadaverous upper extremities, the authors determined the location for resection of the sensitive branch of the volar interosseous nerve that is not associated with the risk of damaged motor innervation of the quadrate pronator muscle. RESULTS: A reliable identification of the motor branches of the volar interosseous nerve was achieved when an approximately 2-cm incision in the interosseous membrane was made 1 cm distal to the passing anterior branch of the interosseous artery that was clearly seen in the operating field. This corresponded to an incision in the skin, leading in the proximal direction at a length of about 7 cm, made 2 cm proximal to the distal radio-ulnar joint. DISCUSSION: The identification of motor branches is often difficult and therefore the authors recommend resection of the sensitive branch of the volar interosseous nerve to be performed in a safe zone that was determined by a large number of anatomical dissections. Partial denervation carried out according to the principles of a physiological procedure does not pose a burden for the patient and can markedly enhance the effect of reconstructive surgery. CONCLUSION: Partial denervation of the wrist performed from the dorsal approach is a simple procedure easy to combine with other reconstructive operations on the wrist.

Adolescent↗

Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts--implications for clinical studies.

To further characterize the behavior of metaiodobenzylguanidine (MIBG) in the myocardium and to test the hypothesis that the denervated heart would show normal early uptake on MIBG due to non-neuronal localization, we examined the early and late distribution of 123I-labeled MIBG in normal and globally denervated canine and human hearts. Canine hearts were denervated by intravenous injections of 6-hydroxydopamine, while patients were studied a mean of 4.3 mo following cardiac transplantation. Results in denervated hearts were compared to normal controls. Normal hearts showed prominent MIBG uptake on initial 5-min and 3-hr delayed images. Globally denervated canine hearts showed prominent uptake on initial images and absence of localization on delayed images, indicating complete washout of non-neuronally bound radionuclide. The transplanted human hearts showed no localization of MIBG on either early or delayed images. These results suggest that the non-neuronal uptake mechanism (uptake 2) is not significant in human myocardium. This finding has significant implications for interpreting the myocardial behavior of MIBG in various pathologic situations such as dilated cardiomyopathy.

3-Iodobenzylguanidine↗

Effects of denervation on the contents of cholesterol and membrane systems involved in muscle contraction in rabbit fast-twitch sarcotubular system.

Denervated fast-twitch rabbit muscles were progressively losing their fresh weight and the yield of sarcotubular protein was increasing. The activity of Ca(2+)-ATPase was affected but very slightly, the basal Mg(2+)-ATPase and the Mg(2+)-ATPase/Ca(2+)-ATPase ratio however increased together with a simultaneous depression of the membrane-bound acetylcholinesterase activity. We did not observe any differences in density properties of sarcotubular fractions between control and denervated muscle. However, a relative enrichment in SM and H fraction could be seen after denervation with small changes in the content of the Ca(2+)-pump protein, increased levels of calsequestrin and cholesterol, mostly in the heavy and the SM fraction. After denervation the binding sites for 3H-PN-200-110 did not show any changes in receptor affinity, but the number of putative Ca(2+)-channels increased twice along with a depression of 3H-ouabain binding sites. We suggest that the denervation of fast-twitch muscle leads to the hypertrophy of the junctional sarcoplasmic reticulum and the T-system. Changes in the cholesterol content, in the number of putative Ca(2+)-channels and in Na+, K(+)-ATPase can affect the muscle contraction.

Acetylcholinesterase↗

Blunting of the renal response to volume expansion by a bradykinin receptor antagonist: influence of denervation.

The interaction of renal sympathetic nervous influences with the intrarenal kallikrein-kinin system was examined during graded expansion of the extracellular fluid volume in rats. One group of rats was pretreated with a specific and highly efficacious competitive antagonist of bradykinin receptor (BKRA), whereas the other group received only a vehicle infusion. The left kidney was denervated in each animal and the right kidney remained intact. After control observations, the extracellular fluid volume was expanded by a continuous i.v. infusion of 0.9% NaCl at a rate of 0.25% of body weight per minute for 40 min (VE). During VE urine flow and sodium excretion increased significantly from both kidneys in each of the two treatment groups. The diuretic response was greatest in the denervated kidneys of vehicle-pretreated rats, where urine flow increased by 70 +/- 13 microliters.min(-1).g kwt(-1). This exaggerated diuresis was blunted by pretreatment with the BKRA. In the denervated and BKRA-treated kidneys, the VE-induced mean urine flow increase was limited to 31 +/- 5 microliters.min(-1).g kwt(-1) (P less than .05 compared with vehicle-pretreated, denervated kidneys). The change in net sodium excretion produced by VE was also reduced by BKRA pretreatment in the denervated kidneys from 13.2 +/- 2.6 to 5.5 +/- 1.3 microEq.min-1.g kwt(-1) (P less than .05, vehicle vs. BKRA). In the intact kidneys the diuretic and natriuretic responses to VE were similar in the vehicle- and BKRA-pretreated rats. Glomerular filtration rate and filtration fraction were increased significantly and to the same extent by VE under all experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Apoptosis in male germ cells induced by testicular denervation].

OBJECTIVE: To evaluate the role of spermatic nerves in the regulation of spermatogenesis. METHODS: Fifty-four mature SD male rats (350-375 g) were randomized into a sham operation group (SO) and three experiment groups, and the latter underwent bilateral surgical removal of the superior spermatic nerve (SSN) or/and the inferior spermatic nerve (ISN). The animals were killed 1 month and 2 months after the operation. HE stain was used to observe spermatogenesis. Transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) were employed to detect apoptosis. RESULTS: Impaired spermatogenesis was observed 2 months after the operation, with only Sertoli cells and a few spermatogonia remaining in the regressed tubules in all the treatment groups. The abnormal tubules in the SSN, ISN and SSN + ISN denervated testes accounted for (13.25 +/- 2.03)%, (11.0 +/- 4.36)% and (34.17 +/- 3.78)% respectively. Chromosome condensation and fragmentation in the germ cells were observed under the electron transmission microscope in all the denervated testes. TUNEL showed the spermatogonia and Leydig cells to be apoptotic in all the denervated testes and the incidence of the apoptotic cells in the SSN + ISN denervated testes was significantly higher than in the SSN or ISN denervated ones. CONCLUSION: Spermatic nerves play an important role in spermatogenesis.

Animals↗

Activation of the ubiquitin-ATP-dependent proteolytic system in skeletal muscle during fasting and denervation atrophy.

The rapid atrophy of skeletal muscles upon fasting or denervation is due largely to an increased rate of protein breakdown. Blocking the lysosomal or the Ca(2+)-dependent pathways did not prevent increased proteolysis in muscles from fasted animals or following denervation. In contrast, upon food deprivation, the nonlysosomal ATP-dependent process increased by 150-350%. After refeeding, this process returned to control levels by 24 h. Similarly, within one day after denervation of the soleus, proteolysis increased by 50-250%. By contrast, the residual energy-independent process did not change in fasting or denervation. Because the ATP-dependent process might involve activation of the ubiquitin-ATP-dependent pathway, we measured the levels of mRNA for ubiquitin [Ub] in the atrophying muscles. After food deprivation, the levels of polyUb transcripts increased 2- to 4-fold in the soleus and extensor digitorum longus (EDL) muscles, and returned to control levels within 1 day of refeeding. After denervation of the soleus, a 2- to 3-fold increase in polyUb mRNA also occurred within 1 day. The muscle content of ubiquitinated protein also changed in parallel with Ub mRNA levels under these conditions. Thus, polyUb genes appear to be selectively induced in atrophying muscle, and levels of Ub mRNA and ubiquitin-protein conjugates change coordinately with the rate of ATP-dependent proteolysis. These data suggest that in atrophying muscle the ATP-Ub-dependent system plays an important physiological role in the degradation of the bulk of cell proteins.

Adenosine Triphosphate↗

[Effects of facial nerve denervation on masseter muscle of the rats].

The effects of unilateral facial nerve denervation on the facial growth were studied by physiological and by histochemical examinations, using four- week- old Wistar rats. Two hundred twenty rats were divided into three groups: a control group, a group of subjects which resection of the left facial nerve, and a sham operation group. The rats were killed 1, 5, 10, 30, 60, 90, 120 days later. The superficial and deep masseter muscle fibers on both sides were classified into type I and type IIA or IIB on the basis of myosin ATPase activity and the diameter of these fibers was measured. The masseter muscles were stained with H&E and NADH-TR. Electromyogram recordings were analyzed during the rest position, stretch reflex, voluntary action and eating of solid foods in half of all groups. (1) The face of rats after denervation deviated to the right side, and the maxillo-facial skeleton was affected from the 30th day. (2) In the denervation groups the right side showed higher action potentials than the left side. (3) In the deep masseter muscles near muscle spindle in the denervated groups, the percentage of type I fibers on the right side increased on the 90th day, and that of type IIA fibers decreased on the 30th day. (4) The diameter of the deep masseter muscle fibers, of type I, IIA and IIB increased on the right side. These results prove that facial nerve denervation led to a functional disorder and a transformation of growing direction.

Action Potentials↗