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PubMed1965

On the differential response of sarcoplasm and myoplasm to denervation in frog muscle.

Electron microscopic evidence is presented that the early response to denervation ("simple atrophy") of the semitendinosus m. of the frog is characterized by a greater prominence of the sarcoplasmic reticulum and by the presence, in the interfibrillar spaces, of mitochondria which are more numerous and smaller than in normal muscle. In contrast with the dynamic changes of the sarcoplasmic structural components, the myofibrils showed a progressive decrease in diameter after denervation and throughout the period studied. By carrying out tissue fractionation experiments, the yield of microsome-protein was found significantly greater in the denervated muscles, as compared with the contralateral controls, in this initial stage. Under the conditions attending the overdevelopment of the sarcoplasmic reticulum (SR), denervated semitendinosus m. incorporated valine-C(14) into proteins more actively than the control pairs. The denervated muscles also showed an increase in the number of freely scattered and membrane-bound ribosomes and of polyribosomes, suggesting a more active synthesis of the SR membranes. Pronounced atrophy of the myofibrils, disorganization of the SR, and an increased number of ribonucleoprotein particles lying in the enlarged interfibrillar spaces were the main ultrastructural features of "degenerative atrophy" in frog muscle in the late periods after denervation. The probably adaptive character of the early changes occurring on denervation of frog muscle is discussed.

Animals↗
PubMed1987

Single channel properties of newly synthesized acetylcholine receptors following denervation of mammalian skeletal muscle.

We have examined the single channel properties of newly synthesized acetylcholine (ACh) receptors in denervated adult mouse muscle. Patch-clamp recordings were made on freshly isolated fibers from flexor digitorum brevis (fdb) muscles that had been denervated in vivo for periods up to 3 wk. Muscles were treated with alpha-bungarotoxin (alpha-BTX), immediately before denervation, in order to block pre-existing receptors. Denervated fibers exhibited two types of ACh receptor channels, which differed in terms of single channel conductance (45 and 70 pS) and mean channel open time (approximately 7 and 2.5 ms, respectively). In contrast to innervated muscle, where only 3% of the total openings were contributed by the low-conductance channel type, greater than 80% of the openings in the nonsynaptic membrane of denervated muscle were of this type. Importantly, a similar increase in the proportion of low-conductance channels was observed for recordings from synaptic membrane after denervation. These data argue against the proposal that, in denervated muscle, the low-conductance channels undergo continued conversion to the high-conductance type focally at the site of former synaptic contact. Rather, our findings provide additional support for the idea that the functional properties of ACh receptors are governed uniformly by the state of innervation of the fiber and not by proximity to the site of synaptic contact.

Animals↗
PubMed1987

Evidence for active chloride accumulation in normal and denervated rat lumbrical muscle.

Intracellular Cl- activity (aiCl) was measured with Cl(-)-sensitive microelectrodes in normal and denervated rat lumbrical muscle. In normal muscle bathed in normal Krebs solution, aiCl lay close to that predicted by the Nernst equation. The addition of 9-anthracene carboxylic acid, which blocks Cl- conductance, caused aiCl to increase far above that predicted by a passive distribution. Furosemide (10 microM) reversibly blocked this accumulation. After muscle denervation, aiCl progressively increased for 1-2 wk. The rise occurred in two stages. The initial stage (1-3 d after denervation) reflected passive Cl- accumulation owing to membrane depolarization. At later times, aiCl continued to increase, with no further change in membrane potential, which suggests an active uptake mechanism. This rise approximately coincided with the natural reduction in membrane conductance to Cl- that occurs several days after denervation. Na+ replacement, K+ replacement, and furosemide each reversibly blocked the active Cl- accumulation in denervated muscle. Quantitative estimates suggested that there was little difference between Cl- flux rates in normal and denervated muscles. The results can be explained by assuming that, in normal muscle, an active accumulation mechanism operates, but that Cl- lies close to equilibrium owing to the high membrane conductance to Cl-. The rise in aiCl after denervation can be accounted for by the membrane depolarization, the reduction in membrane Cl- conductance, and the nearly unaltered action of an inwardly directed Cl- "pump."

Animals↗
PubMed2004

NGF, BDNF, NT-3, and GDNF mRNA expression in rat skeletal muscle following denervation and sensory protection.

Poor muscle and nerve functional recovery after nerve damage is a serious clinical problem, particularly if there is prolonged delay before nerve-muscle contact is reestablished. Our previous studies showed that sensory nerve cross-anastomosis (sensory protection) provides support to the denervated muscle. In the present study, we analyzed neurotrophic factor mRNA expression by RT-PCR in denervated rat gastrocnemius muscle receiving sensory protection with the saphenous nerve, compared to normal innervated muscle, to denervated muscle, and to denervated muscle repaired immediately with the peroneal (motor) nerve, after periods of 3 days to 3 months. No significant differences in mRNA levels of beta-actin, nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3 were found between the sensory protection treatment and the denervated or the motor repair groups. However, sensory protection resulted in levels of muscle glial cell line-derived neurotrophic factor mRNA expression that were lower than in denervated muscle and higher than in muscle given immediate motor repair. These results demonstrate that glial cell line-derived neurotrophic factor mRNA is elevated following denervation but is partially down-regulated by sensory protection. Our study suggests that sensory protection provides a modified trophic environment by modulating neurotrophic factor synthesis in muscle.

Actins↗
PubMed2005

Electrical stimulation attenuates denervation and age-related atrophy in extensor digitorum longus muscles of old rats.

Skeletal muscles of old rats and elderly humans lose muscle mass and maximum force. Denervation is a major cause of age-related muscle atrophy and weakness, because denervated fibers do not contract, and undergo atrophy. At any age, surgical denervation causes even more dramatic muscle atrophy and loss in force than aging does. Electrical stimulation that generates tetanic contractions of denervated muscles reduces the denervation-induced declines. We investigated whether a stimulation protocol that maintains mass and force of denervated extensor digitorum longus muscles of adult rats would also maintain these properties in denervated muscles of old rats during a 2-month period of age-induced declines in these properties. Contractile activity generated by the electrical stimulation eliminated age-related losses in muscle mass and reduced the deficit in force by 50%. These data provide support for the hypothesis that during aging, lack of contractile activity in fibers contributes to muscle atrophy and weakness.

Aging↗
PubMed2004

Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration?

Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES, and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 +/- 14.8 SD (p < 0.0001 vs DDM 14.9 +/- 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 +/- 5.7 SD (p < 0.0001 vs DDM 25.7 +/- 23.7 SD); the mean percentile fat area is 2.1 +/- 2.4 SD (p < 0.001 vs DDM 12.8 +/- 12.1 SD); and the mean percentile connective tissue area is 3.6 +/- 4.6 SD (p < 0.001 vs DDM 61.6 +/- 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter smaller than 10 microm, while the FES-trained subjects have more that 50% of myofibers larger than 30 microm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.

Action Potentials↗
PubMed1983

Increase in norepinephrine-induced formation of phosphatidic acid in rat vas deferens after denervation.

Surgical denervation of rat vas deferens causes supersensitivity in that the tissue sensitivity and the maximum response to a variety of agonists increase. To understand the molecular mechanism of supersensitivity in smooth muscle, norepinephrine(NE)-induced alteration in phospholipid metabolism was studied using control and denervated vasa deferentia. When the tissue was stimulated by NE, only [32P]Pi incorporation into phosphatidic acid(PA) was increased in proportion to the increase in NE concentration without any significant effect on that into other phospholipids. This PA labeling was significantly accelerated by denervation. In the denervated tissue, PA labeling was stimulated by lower concentrations of NE and the maximum response to NE was increased compared to the control. The breakdown of phosphatidylinositol 4-monophosphate(DPI) and phosphatidylinositol 4,5-diphosphate (TPI) was also accelerated by NE. But the influence of denervation on this NE-induced DPI and TPI was not marked. Therefore, it is likely that denervation clearly enhanced NE-induced PA labeling without an appreciable effect on that of the other phospholipids. Furthermore, the absolute amount of PA was also increased by NE, and this increase was exaggerated by denervation. Considering that PA can behave as a Ca2+ ionophore in the plasma membrane, these results suggest that the stimulated accumulation of PA plays an important role in receptor-linked supersensitivity in smooth muscle.

Animals↗
PubMed2002

Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats.

PURPOSE: During inspiration, recruitment of the intrinsic laryngeal muscles (ILM) reduces the inspiratory load on the ventilatory pump muscles. The purpose of our study was to determine 1) whether the diaphragm adapts to denervation of the ILM, and 2) whether the additional stimulus of exercise training affects the degree to which the diaphragm adapts to ILM denervation. METHODS: Thirty-six male Sprague-Dawley rats (2 months) were randomly divided into sedentary control (SC), sedentary-denervated (SD), and exercise-denervated (ED) groups. Control animals underwent sham operations, whereas ILM-denervated animals underwent bilateral transection of the recurrent laryngeal nerves. Three weeks after surgery, animals in the ED group performed a treadmill training protocol for a period of 6 wk. RESULTS: Denervation (SD and ED animals) of the ILM significantly increased diaphragm citrate synthase activity (20%), in vitro endurance, and time to peak twitch tension (15%), and reduced (13%) peak tetanic tension (Po, N x cm(-2)). No independent training effect over and above the effects attributed to denervation of ILM were noted in ED animals. CONCLUSION: The results highlight the role of vocal cord dilator function during both eupnea and exercise-induced hyperpnea.

Adaptation, Physiological↗
PubMed1996

Delay of the denervation process in skeletal muscle by sensory ganglion graft and its clinical application.

We examined the effects of dorsal root ganglion isografts on the denervation process of skeletal muscle. A segment of sciatic nerve was removed from each of 25 inbred Wistar-Kyoto rats. Fifteen were set aside as controls. In the remaining 10 rats, isogeneic cervical dorsal root ganglia were grafted to the severed distal stump of the common peroneal nerve. Between day 72 and day 286 postoperatively, both controls and recipients were killed after twitch and tetanic tension recording of the extensor digitorum longus was performed. The wet muscle weight and the twitch and tetanic tensions of the denervated extensor digitorum longus in the graft group were significantly greater than those in the control group. The mean area of the denervated tibialis anterior muscle fibers in the graft group also was significantly larger than that in the control group. In electron and light microscopic images, nerve cells along the periphery of each dorsal root ganglion were found surviving with regenerating axons throughout the experimental period. Numerous myelinated axons were observed in the common peroneal nerve of the graft group, and there were significantly more axonal branches in the extensor digitorum longus of the graft group than in the extensor digitorum longus of the control group. Thus sensory nerve fibers from the grafted dorsal root ganglia had certain beneficial effects to slow the denervation process, presumably secreting trophic factors into the denervated muscle. Clinically, we have transferred avulsed dorsal root ganglia in cases of total brachial plexus avulsion directly into denervated skeletal muscle. This procedure, accompanied by nerve crossing procedures, will probably keep denervated skeletal muscle in a better condition until regenerating motor axons from the repair site reach their target muscle.

Animals↗
PubMed2003

Denervated muscle fibers explain the deficit in specific force following reinnervation of the rat extensor digitorum longus muscle.

The authors tested the hypothesis that, after denervation and reinnervation of skeletal muscle, observed deficits in specific force can be completely attributed to the presence of denervated muscle fibers. The peroneal nerve innervating the extensor digitorum longus muscle in rats was sectioned and the distal stump was coapted to the proximal stump, allowing either a large number of motor axons (nonreduced, n = 12) or a drastically reduced number of axons access to the distal nerve stump (drastically reduced, n = 18). A control group of rats underwent exposure of the peroneal nerve, without transection, followed by wound closure (control, n = 9). Four months after the operation, the maximum tetanic isometric force (Fo) of the extensor digitorum longus muscle was measured in situ and the specific force (sFo) was calculated. Cross-sections of the muscles were labeled for neural cell adhesion molecule (NCAM) protein to distinguish between innervated and denervated muscle fibers. Compared with extensor digitorum longus muscles from rats in the control (295 +/- 11 kN/m2) and nonreduced (276 +/- 12 kN/m2) groups, sFo of the extensor digitorum longus muscles from animals in the drastically reduced group was decreased (227 +/- 15 kN/m2, p < 0.05). The percentage of denervated muscle fibers in the extensor digitorum longus muscles from animals in the drastically reduced group (18 +/- 3 percent) was significantly higher than in the control (3 +/- 1 percent) group, but not compared with the nonreduced (9 +/- 2 percent) group. After exclusion of the denervated fibers, sFo did not differ between extensor digitorum longus muscles from animals in the drastically reduced (270 +/- 20 kN/m2), nonreduced (301 +/- 13 kN/m2), or control (303 +/- 10 kN/m2) groups. The authors conclude that, under circumstances of denervation and rapid reinnervation, the decrease in sFo of muscle can be attributed to the presence of denervated muscle fibers.

Animals↗
PubMed1986

Chronic stimulation modifies the isotonic shortening velocity of denervated rat slow-twitch muscle.

Rat soleus muscles were denervated and stimulated in vivo for periods of up to 104 days. Stimuli used were trains of 1 ms pulses at 100 Hz delivered for periods of 1 s; trains were repeated every 10-100 s. In a majority of animals the tension of the muscles was maintained at about 10% of normal, equivalent to muscles denervated but unstimulated for 20 days. At the longest periods the stimulated muscles developed ten times more tension than ones that were denervated but not stimulated. In denervated and denervated-stimulated muscles twitch contraction and relaxation times were prolonged, compared with controls, for up to 3 weeks. Thereafter both sets showed a speeding of the isometric twitch that was greater in the stimulated muscles. At the longest periods the twitch was as short as that of a denervated fast muscle. Stimulation did not affect contralateral denervated muscles. Twitch: tetanus ratios remained high despite stimulation, and muscles showed little post-tetanic potentiation. Tension developed more rapidly in the tetani of the stimulated muscles, even allowing for larger final values. Maximum velocity of shortening was increased in many of the stimulated muscles, and there was a proportional flattening of the force-velocity curve, i.e. a/P0 increased. Maximum velocity and a/P0 increased reciprocally with twitch time to peak, so that those muscles that had twitches most changed by stimulation also had their isotonic properties modified to the greatest extent. Even at the longest period of stimulation, twitch time course and tetanic tension were not converted to those of normal fast muscle.

Animals↗
PubMed1994

Parvalbumin immunohistochemistry in denervated skeletal muscle.

Parvalbumin is a calcium-binding protein which, in muscle, is mainly found in type 2B fibres, whereas type 1 fibres lack parvalbumin immunoreactivity. Previous studies have shown that this pattern is highly dependent upon motor neuron innervation and is modified in denervated, cross-reinnervated or chronic low-frequency stimulated muscles. In the present study, we have examined the modifications of parvalbumin immunocytochemistry in the anterior tibialis muscle of the rat at different intervals following section of the sciatic nerve. During the first 2 weeks after denervation, no changes in parvalbumin immunoreactivity were seen, although a global reduction of fibre diameter was observed. Three weeks after denervation, small angulated, strongly parvalbumin-immunoreactive fibres appeared. From the second month onwards, the pattern of parvalbumin immunohistochemistry was characterized by areas composed of small, strongly immunoreactive fibres separated by less atrophic areas displaying a normal chequerboard distribution of parvalbumin immunoreactivity. The increase of parvalbumin-immunoreactivity in denervated and reinnervated muscle, as seen in our study, indicates that important changes in parvalbumin distribution occurs in muscle fibres after denervation. These changes are probably produced in an attempt to bind the free cytosolic calcium which accumulates in denervated fibres, and further reinforces the role of parvalbumin in calcium homeostasis during denervation and reinnervation.

Adenosine Triphosphatases↗
PubMed1996

Expression of myosin isoforms in denervated, cross-reinnervated, and electrically stimulated rabbit muscles.

The expression of myosin heavy (MyHC) and light (MyLC) chain isoforms was analyzed after denervation and cross-reinnervation by a fast nerve of the slow-twitch Semimembranosus proprius (SMp) muscle, and after denervation and electrical stimulation at low frequency of the fast-twitch Semimembranous accessorius (SMa) muscle of the rabbit. The control SMp (100% type I fibers) expressed 100% type I MyHC and 100% slow-type (1S', 1S and 2S) MyLC isoforms. Five month denervation did not alter significantly the MyHC expression of the muscle, but induced the expression of a new type 1 MyLC corresponding most probably to an embryonic MyLC. Five-month cross-reinnervation of the SMp by the fast SMa nerve induced a large change of its fiber type properties. As shown by immunocytochemistry, almost all fibers were stained by fast myosin antibody, but a high proportion of them co-expressed slow myosin. This result was in agreement with biochemical data showing that fast MyHC and MyLC isoforms became predominant. The control SMa (nearly 100% type II fibers) expressed almost 100% type II MyHC (70% type IIb and 22% IIx/d) and 100% fast-type (1F, 2F and 3F) MyLC isoforms. Five month denervation of the SMa induced a shift in its MyHC, with 98% type IIx/d and 2% type IIb isoforms, and no change in the proportions of its MyLC. Three month electrical stimulation at 10 Hz of the SMa transformed its fiber type composition. All fibers reacted with the slow myosin antibody and a minor proportion of them were stained by the fast myosin antibody. These observations were in agreement with the biochemical analysis showing a large predominance of the slow-type MyHC and MyLC isoforms. Taken together, these results obtained from rabbit muscles which are normally homogeneous in either fast-twitch or slow-twitch fiber types, further support the idea that the different myosin isoforms, particularly the MyHC, are differentially regulated by motor innervation. Type I MyHC is maintained in denervated SMp muscle, but is not expressed in denervated SMa. Type IIb isoform is the most sensitive to neural influence, as it disappears rapidly in denervated and electrically stimulated fast-twitch SMa muscle, and is barely expressed in cross-reinnervated slow-twitch SMp muscle. In contrast, type IIa and type IIx/d are less dependent upon motor innervation. In addition to the previous studies of d'Albis et al. analysis of these results leads us to conclude that, in the rabbit, sensitivity to motor innervation increases from the glycolytic to the oxydative types of fibers, in the order IIB > IIX/IID > IIA > I.

Animals↗
PubMed1989

Effects of renal denervation and atrial natriuretic factor on tubular reabsorption in anaesthetized rats.

1. The effects of acute unilateral renal denervation were examined in 17 anaesthetized rats. Renal haemodynamic changes were monitored using standard clearance techniques. Lithium clearance was used to assess fractional proximal sodium and water reabsorption. 2. Denervation resulted in ipsilateral renal vasodilatation with marked natriuresis and diuresis, a small increase (15%, P less than 0.05) in glomerular filtration rate (GFR) and a consequent reduction in filtration fraction. Fractional lithium reabsorption decreased (67.3 +/- 2.9% to 54.5 +/- 4.0%, P less than 0.01) and absolute proximal reabsorption did not change, indicating impairment of proximal glomerulotubular balance (GTB). No similar changes in haemodynamic or transport parameters were observed in the contralateral, innervated kidney, although vascular resistance increased. 3. In 9 experiments following denervation of the left kidney, systemic low dose infusion (10 ng/min) of atrial natriuretic factor (ANF) resulted in a fall in mean arterial blood pressure from 116 +/- 3 mmHg to 107 +/- 3 mmHg (P less than 0.05). In the denervated kidney ANF increased urine flow rate and sodium excretion to rates above those established following denervation alone. However, in the right kidney, despite the increased filtered load (35%, P less than 0.01), the natriuretic and diuretic responses to ANF were abolished. 4. In the denervated kidney, ANF further reduced the fractional reabsorption of lithium from 53.6 +/- 2.3% to 45.6 +/- 3.8% (P less than 0.05). GFR increased by 32% (a total of 49% higher than during pretreatment) but absolute proximal reabsorption (APR) did not change. However, in the right, innervated kidney ANF infusion produced a 35% increase in GFR accompanied by a 53% rise in APR. 5. It is concluded that the natriuresis induced by unilateral denervation is due predominantly to impaired proximal GTB. The natriuretic action of ANF was associated with further impairment of proximal GTB, not dependent upon decreasing activity of renal sympathetic nerves, but was abolished when filtration fraction and renal sympathetic tone were elevated.

Absorption↗
PubMed2005

Denervation-induced alterations in gene expression in mouse skeletal muscle.

Motoneurons are important for regulating the function and properties of skeletal muscle. In the present study high-density oligonucleotide arrays have been used to compare gene expression in innervated and six-days denervated NMRI mouse skeletal muscle. To avoid looking at genes mainly participating in the process of atrophy, both hind-limb muscles (atrophic after denervation) and hemidiaphragm muscle (transiently hypertrophic after denervation) were used. Only genes previously not known to respond to denervation and with potential roles in DNA/RNA interactions/transcription and/or cellular communication/signalling are presented. Data for additional genes are provided as supplementary material. Thirty-two genes, up-regulated by a factor of two or down-regulated to the same extent after denervation, are presented. These include genes that may act through chromatin remodelling and/or as transcription factors/regulators (Cdkn1a, Cdr2, Hrmt1l2, Idb2, Myc/c-myc, L-myc1, Rb1, Sap30 and Tgif), genes possibly involved in the regulation of muscle membrane properties and/or excitation-contraction coupling (Cacng1, Camk2d, Hrmt1l2, Kcnj12, Kcna7 and Rrad) and genes potentially involved in neuromuscular interactions and/or receptor signalling (Acvr2b, Adam19, D0H4S114, Kai1, Maged1, Mt2, Prkcabp, Ptp4a3, Ramp1, Rras, Timp1, Vegfa and Zfp145). A set of five genes with altered expression after denervation (Fzd9, Nr4a1, Frat2, Ctgf and Cyr61) indicate that Wnt signalling may be reduced in denervated skeletal muscle.

Animals↗
PubMed1995

Effects of denervation on muscarinic receptors in the rat bladder.

OBJECTIVE: To demonstrate the specific distribution of muscarinic receptors in the rat urinary bladder and to investigate the effects of afferent and efferent denervation on the density and distribution of muscarinic receptors. MATERIALS AND METHODS: Urinary bladders were obtained from female rats which had been injected with vehicle (control), or neonatally with capsaicin (NC, afferent denervation) or which had their pelvic plexus removed (post-ganglionic denervation, PGD, efferent denervation). Tissue sections were used in radioligand-binding studies and for autoradiography with the muscarinic receptor ligand l-quinuclidinyl[phenyl-4-3H]benzilate (QNB). RESULTS: Binding of QNB was saturable and specific to a single population of binding sites, with a mean dissociation constant (Kd) of 1.05 +/- 0.14 nM in controls and 0.90 +/- 0.13 nM in rats with PGD. Post-ganglionic denervation caused a 37% increase in maximal binding (Bmax) of QNB from 437.1 +/- 39.1 fmol/mg protein (control group) to 599.1 +/- 4.5 fmol/mg protein (P < 0.02). Autoradiograms revealed muscarinic binding sites over the smooth muscle, but none over the epithelium. Smooth muscle binding sites were doubled after PGD but were unchanged after NC treatment. CONCLUSION: Muscarinic receptors were localized over the smooth muscle of the rat bladder and were increased after post-ganglionic denervation. This increase may be responsible for the increased sensitivity to muscarinic agonists reported to occur after bladder denervation.

Animals↗
PubMed1999

Contribution of baroreceptors and chemoreceptors to ventricular hypertrophy produced by sino-aortic denervation in rats.

1. To test whether sino-aortic denervation (SAD)-induced right ventricular hypertrophy (RVH) is a consequence of baroreceptor or chemoreceptor denervation, we compared the effects of aortic denervation (AD), carotid denervation (CD), SAD and a SAD procedure modified to spare the carotid chemoreceptors (mSAD), 6 weeks after denervation surgery in rats. A sham surgery group served as the control. 2. The blood pressure (BP) level was unaffected by AD, CD or SAD, but increased (9 %) following mSAD. The mean heart rate level was not affected. Short-term BP variability was elevated following AD (81 %), SAD (144 %) and mSAD (146 %), but not after CD. Baroreflex heart rate responses to phenylephrine were attenuated in all denervation groups. 3. Significant RVH occurred only following CD and SAD. These procedures also produced high mortality (CD and SAD) and significant increases in right ventricular pressures and haematocrit (CD). 4. Significant left ventricular hypertrophy occurred following CD, SAD and mSAD. Normalized left ventricular weight was significantly correlated with indices of BP variability. 5. These results suggest that SAD-induced RVH is a consequence of chemoreceptor, not baroreceptor, denervation. Our results also demonstrate that a mSAD procedure designed to spare the carotid chemoreceptors produced profound baroreflex dysfunction and significant left, but not right, ventricular hypertrophy.

Adrenergic alpha-Agonists↗
PubMed2001

Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow.

A novel method of renal denervation was developed based on electro-coagulation of tissue containing most of the sympathetic fibres travelling towards the kidney. Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the contralateral innervated kidney when studied 3 days postdenervation. The method was utilised in anaesthetised rats to examine the effects of denervation within the heretofore unexplored first 75 min period postdenervation. Sodium excretion (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after denervation. In a parallel group, with a lower baseline UNaV, there was also a significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal perfusion pressure was maintained at a constant value and the glomerular filtration rate did not change after denervation. Renal cortical and medullary blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue ion concentration was estimated as electrical admittance (Y). Following denervation, in both groups CBF increased significantly within the first 25 min (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or decreased slightly; Y did not change. The data document the development of natriuresis within the first 25-50 min after denervation. The increase in CBF indicated that, prior to denervation, the cortical, but not medullary, circulation was under a tonic vasoconstrictor influence of the renal nerves. Such a dissociation of neural effects on the renal cortical vs. medullary vasculature has not been previously described.

Animals↗