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PubMed1983

Effect of denervation on the hepatic haemodynamic response to hypercapnia and hypoxia in the dog.

The effect of hepatic and mesenteric arterial denervation on the hepatic haemodynamic response to hypercapnia and hypoxia was studied in 13 pentobarbitone anaesthetized greyhounds. Electromagnetic flowmeters were used to measure blood flow in the hepatic artery (HA) and portal vein (PV). Hypercapnia of 100 mm Hg PaCO2 increased PV blood flow and decreased HA blood flow, with opposite changes in mesenteric and HA vascular resistances. All parameters tended to return slightly towards baseline with extended periods of hypercapnia. HA denervation eliminated the changes in HA flow and resistance, while mesenteric arterial denervation appeared to prevent the secondary changes in PV blood flow and mesenteric vascular resistance. It is concluded that the sympathetic nervous system is responsible for the HA vasoconstriction observed during hypercapnia and that it exerts a delayed slight inhibitory influence on a predominantly direct vasodilatory effect of carbon dioxide on the mesenteric vasculature. Hypoxia of 40 mm Hg PaO2 produced sustained increases in HA and mesenteric vascular resistances and a small increase in PV blood flow, together with a pronounced increase in systemic arterial blood pressure. HA denervation eliminated the HA resistance increase and caused the HA blood flow to increase during hypoxia. Mesenteric arterial denervation prevented the increases in mesenteric resistance. PV flow and arterial blood pressure from being sustained throughout the hypoxic period. It is concluded that hypoxia produces a sympathetically mediated mild vasoconstriction of both the HA and mesenteric vascular systems.

Animals↗
PubMed1987

A study on early post-denervation changes of non-quantal and quantal acetylcholine release in the rat diaphragm.

The d-tubocurarine (dTC) induced hyperpolarization of antiesterase-treated muscles at the endplate zone, miniature endplate potentials (mepps), resting membrane potentials (RMPs) and the input resistances of single muscle fibres (Rin) were measured in rat diaphragm at various times after denervation. The dTC-induced hyperpolarization decreased in two phases: 2 h after denervation it decreased transiently to 25%, after 4 h it had partially recovered to 60% and from 6 h it progressively decreased up to 12 h after which time it changed to depolarization. The initial fall and recovery were also present in muscles from sham-operated animals. The frequency of mepps decreased by 25% and the amplitude diminished by 10% within the first 2-4 h. After 10 h the frequency had decreased by 35% and the amplitude by 65%. After 12 h no mepps were present. The RMP was not significantly changed during the first 16 h after denervation. From 16 to 24 h the membrane became depolarized at a rate of about 1 mV/h. The input resistance of a single muscle fibre was constant for 12 h after denervation and from 12 to 24 h it increased by 25%. It is concluded that the early decrease in the dTC-induced hyperpolarization is probably due to the desensitization of acetylcholine (ACh) receptors caused by stress-activated non-quantal ACh release. The later decrease of dTC-hyperpolarization reflects a fall in the non-quantal ACh release. The depolarization of the resting membrane after denervation is related to the decrease in passive membrane permeability which is a secondary consequence of transmission failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

Acetylcholine-sensitivity and local regenerative activity in denervated frog slow muscle fibres.

The distribution of acetylcholine (ACh)-sensitive membrane areas was determined in 11-75 days denervated slow muscle fibres of Rana temporaria by iontophoretic application of acetylcholine. The fibres were also stimulated directly, and their electrical activity was recorded with an intra- and an extracellular electrode. During the first two weeks following denervation the size of the ACh-sensitive fibre surface was similar to that of normal slow fibres, but a spreading out of ACh-sensitivity occurred between the 13th and 20th day. The slow fibre membrane did not become homogeneously ACh-sensitive; even after long periods of denervation large local sensitivity gradients could be observed. Throughout the denervation period maximum values of ACh-sensitivity were in the same range as in normal slow fibres. Action potentials were fully developed when ACh-sensitivity started to spread out. Extracellularly recorded inward currents varied in amplitude along the fibre surface, and either one or two peaks were observed in individual fibres. The spatial relationship between inward current peaks and peaks of ACh-sensitivity was investigated in 12 fibres. Fifteen inward current peaks were located at distances of 30-640 microns from points of maximum ACh-sensitivity; only once did the centers of ACh-sensitivity and excitability coincide. It is concluded that Na channels are incorporated into nonjunctional membrane areas of denervated slow fibres; this process precedes the incorporation of ACh receptors by approximately one week.

Acetylcholine↗
PubMed1985

Changes in the ionic currents sensitivity to inhibitors in twitch rat skeletal muscles following denervation.

Under voltage clamp conditions, using the double mannitol gap technique, ionic currents developed by fast (e.d.l.) and slow (soleus) twitch muscle fibers of the rat were analysed at different times following denervation and the results compared with those obtained in normal cells. In slow fibers, denervation caused the appearance of a new population of TTX-resistant Na+ channels (dissociation constant K2 = 2,800 nM) compared with the normal TTX-sensitive Na+ channels (K1 = 9 nM). This new population of Na channels appeared in 5 days and contributed about 32% of the total Na conductance. Denervated fast fibres developed a slow component in the delayed outward current which was found to be typical of slow innervated muscles. This component appeared 5 to 20 days after nerve section. These changes are associated with modifications of potassium channels' sensitivity for specific inhibitors (TEA and 4-AP). After denervation, the delayed outward current in the two types of muscles becomes resistant to 4-AP whereas TEA, which blocks the total delayed outward current in innervated fibers (dissociation constant of 21.4 mM) becomes more effective in blocking the fast component (dissociation constant of 0.61 mM) and less effective in blocking the slow component in denervated cells. The analysis of the characteristics of the TEA sensitive and TEA insensitive components of the outward current leads to the proposal that these components were related to the fast and to the slow components previously described in fast and slow twitch mammalian skeletal muscles.

4-Aminopyridine↗
PubMed1986

Renal sodium handling in intact and renal denervated dogs.

The ability to retain sodium was investigated in six conscious dogs before and after surgical renal denervation. Dietary sodium and water intake were kept constant (2.5 mmol Na X kg-1 bw X day-1 and 91 ml water X kg-1 bw X day-1). Balance experiments were performed from 6 days before to 8 days after having produced a sodium deficit of 6.4 +/- 0.4 (intact dogs) and 5.8 +/- 0.2 (renal denervated dogs) mmol Na X kg-1 bw by means of a peritoneal dialysis (PD). Having the same sodium excretion before PD, intact and renal denervated dogs demonstrated a similar striking decrease of sodium excretion and a similar increase of plasma renin activity after PD until the amount of sodium lost had been replenished (4th day after PD). In intact and renal denervated dogs plasma sodium concentration (PNa) decreased and renal water excretion increased on the first day after PD, indicating a homeostatic response to the fall of PNa. After dietary sodium restriction (from 2.5 to 0.5 mmol Na X kg-1 bw X day-1) a similar striking decrease of renal sodium excretion occurred in intact and renal denervated dogs. It therefore is concluded that in conscious dogs the presence of the renal nerves is not essential in order to maintain body sodium homeostasis after an acute sodium loss or after dietary sodium restriction.

Animals↗
PubMed1981

Acetylcholine receptor concentration in the mimic musculature of the rat following denervation and reinnervation.

The facial musculature of the rat was denervated by cutting the facial nerve. Over a period of 41 days no facial movements were observed. Acetylcholine receptor concentrations, determined by [125I]-alpha-bungarotoxin binding, increased sharply in the early stage of denervation (at day 10) and were still significantly higher than in the controls after 41 days. When cutting of the facial nerve was followed by immediate nerve repair (primary suture), facial movements returned on about day 16. The receptor concentrations reflected changes monitored by clinical observations. At day 10, when denervation of the facial muscles was still complete, receptor concentrations corresponded to those found in the permanently denervated muscles. At day 16 the reinnervated muscles of half the animals displayed muscle activity and had receptor concentrations identical to those found for normal (control) tissue. The other half of the animals, with no muscular activity detectable, had receptor concentrations as high as in permanently denervated tissue. After 23 days the receptor concentrations had essentially decreased to control levels and all rats had regained complete facial function.

Animals↗
PubMed1992

Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: a possible role for myogenin in denervation supersensitivity.

1. We have prepared probes specific for the chicken myogenic determination genes MyoD, myogenin, myf5, and herculin and have investigated the expression of these genes in response to denervation and acute electrical stimulation in neonate chick muscle, using ribonuclease protection. 2. Upon denervation, herculin mRNA remains essentially unchanged, myf5 transcript levels approximately double, and MyoD message is up-regulated by two- to fivefold. In contrast, the message coding for myogenin, barely detectable in innervated muscle, rises dramatically (approximately 200-fold) on the second day after nerve section; in this respect it resembles acetylcholine receptor (AChR) alpha-, gamma- and delta-subunit mRNAs. Cohybridization experiments reveal that the increase in myogenin mRNA slightly precedes the rise in AChR alpha-subunit message. 3. Electrical stimulation of denervated muscle leads to an immediate decline in myogenin and AChR alpha-subunit mRNAs, with half-lives of less than an hour and approximately 4 hr, respectively; message stability measurements suggest that this is effected through a rapid shutdown of transcription. Messages coding for MyoD, myf5, and herculin decay much more slowly, as a result of slower turnover. 4. Previous experiments have indicated the involvement of a de novo induced (Tsay, H.-J., Neville, C. M., and Schmidt, J., FEBS Lett. 274:69-72, 1990) autocatalytic (Neville, C. M., Schmidt, M., and Schmidt, J., NeuroReport 2:655-657, 1991) transcription factor in the denervation-triggered up-regulation of AChR alpha-subunit expression; the denervation and electrical stimulation experiments reported here are compatible with the notion that myogenin is that factor.

Amino Acid Sequence↗
PubMed1988

Calcium binding protein changes of sarcoplasmic reticulum from rat denervated skeletal muscle.

Two Ca2+ sequestering proteins were studied in fast-twitch (EDL) and slow-twitch (soleus) muscle sarcoplasmic reticulum (SR) as a function of denervation time. Ca2+-ATPase activity measured in SR fractions of normal soleus represented 5% of that measure in SR fractions of normal EDL. Denervation caused a severe decrease in activity only in fast-twitch muscle. Ca2+-ATPase and calsequestrin contents were affected differently by denervation. In EDL SR, Ca2+-ATPase content decreased progressively, whereas in soleus SR, no variation was observed. Calsequestrin showed a slight increase in both muscles as a function of denervation time correlated with increased 45Ca-binding. These results indicate first that Ca2+-ATPase activity in EDL was under neural control, and that because of low Ca2+-ATPase activity and content in slow-twitch muscle no variation could be detected, and secondly that greater calsequestrin content might represent a relative increasing of heavy vesicles or decreasing of light vesicles as a function of denervation time in the whole SR fraction isolated in both types of muscles.

Animals↗
PubMed1991

Molecular alterations in the perijunctional region of frog skeletal muscle fibres following denervation.

The anatomical distribution of a frog skeletal muscle antigen was studied using immunofluorescence microscopy and a monoclonal antibody 3B6 that was produced against denervated skeletal muscle. In innervated muscles, the monoclonal antibody 3B6 stain was associated with the inner surface of the muscle plasma membrane at the endplate and myotendinous junction. After denervation, the monoclonal antibody 3B6 stain extended from the endplate laterally around the perimeter of muscle fibres and longitudinally well beyond the endplate for a total length of 600-1000 microns. The monoclonal antibody 3B6 stain thus forms a cylindrical structure centred on the endplate. This observation shows that denervation produces a non-homogeneous molecular change in skeletal muscle fibres: an antigen that is present in high concentrations at innervated endplates appears in restricted perijunctional regions of denervated muscle fibres. It further suggests that perijunctional regions of denervated muscle fibres differ from the remaining non-endplate regions in molecular composition and possibly also in function.

Animals↗
PubMed1993

Fibre type specific expression of Leu19-antigen and N-CAM in skeletal muscle in various stages after experimental denervation.

Leu-19 antigen, which seems to be identical with neural cell adhesion molecule (N-CAM), plays a major role in the innervation of muscle cells, and in adult muscle appears after denervation and during regeneration of muscle fibres, where it acts as part of a signalling system increasing the probability of re-innervation. This combined enzyme-histochemical and immunohistochemical study examined whether this signalling process was regulated in a uniform or differential pattern for type 1 and type 2 muscle fibres. The subscapular nerve of 18 rabbits was transsected with subsequent complete denervation of the supraspinatus muscle. Leu-19 and N-CAM immunohistochemistry was performed 2 to 64 days after surgery. Whereas in normal muscle there are virtually no Leu-19/N-CAM positive muscle fibres; from day 2 after denervation an increasing proportion of fibres expressed Leu-19/N-CAM, prior to any neurogenic atrophy. In the early stage of denervation Leu19/N-CAM expression was confined to type 1 fibres. After 11 days nearly all fibres were Leu19/N-CAM positive irrespective of their fibre type. Sixty-four days after denervation type 1 fibres became Leu19/N-CAM negative, while atrophic type 2 fibres showed intensive staining. Thus, expression of Leu-19 antigenicity is differently regulated in both fibre types.

Animals↗
PubMed1998

Dipole source localization by mottled sculpin. III. Orientation after site-specific, unilateral denervation of the lateral line system.

To test the hypothesis that spatial excitation patterns along the lateral-line system underlie source localization, we videotaped the orientation behavior of blinded mottled sculpin in response to a small dipole source (50-Hz vibrating sphere) before and after unilateral denervation of the lateral line system on different body regions (head, trunk and head + trunk). Approach pathways were qualitatively similar to those followed by normal intact animals. Abnormal behavior (turning in circles) was not observed. However, the frequency with which fish placed their intact side facing the source increased by 12-89%, depending on the denervation site. The angular accuracy of orientation decreased by 20 degrees to 60 degrees (100% to 370% change) depending on source location and region of lateral line denervated. Deficits tended to be site-specific. For example, unilaterally denervating lateral-line organs on the head resulted in less accurate orienting responses when the source was located on the denervated side of the head, but not on the opposite side of the head or on either side of the trunk. Site-specific deficits and the absence of abnormal approach pathways argue that animals are relying on a point-by-point spatial representation of source location along the sensory surface rather than computations based on bilateral comparisons.

Animals↗
PubMed1997

Denervation-induced region-specific changes in fibre types in the soleus and plantaris muscles of rats.

Muscle fibre composition was compared among the proximal (25%), middle (50%) and distal (75%) regions of muscle to investigate whether denervation induces region-specific changes of fibre types in the soleus and plantaris muscles of rats. Decreases in mass were observed in both muscles after denervation. In the soleus muscle, denervation increased the percentage of type I fibres with a concomitant increase in the proportion of type IIC and IIA fibres. The extent of such transformations was greater in the proximal region than the middle and distal regions. In normal plantaris muscle, the middle region showed a higher proportion of type IIA fibres with a lower percentage of type IIB fibres reciprocally than other regions. These regional differences in fibre types were not detected in the 4-week denervated plantaris muscle. These findings suggest that denervation-induced transformations from type I to type II fibres begin in the proximal region in the soleus muscle of rats. In addition, regional differences in fibre types along the muscle length could be regulated by neuromuscular activity through normal innervation in the plantaris muscle.

Animals↗
PubMed1994

Effects of cardiac denervation on coronary and systemic circulation.

The effects of cardiac denervation on coronary circulation and systemic hemodynamics were examined in patients who underwent coronary artery bypass grafting for a totally occluded left anterior descending coronary artery. The results in 14 patients who had undergone a combination of bypass grafting and intrapericardial denervation (group I) were compared with those in 19 patients who had undergone only bypass grafting (group II). The heart rate was 110 +/- 4.9 beats/min in group I and 104 +/- 3.7 beats/min in group II after denervation. Although the cardiac index was not significantly different between the two groups, the calculated systemic vascular resistance index of group I (1,358 +/- 111 dynes.s.cm-5.m2) was significantly lower (p < 0.02) than that in group II (1,713 +/- 75 dynes.s.cm-5.m2). The end-diastolic coronary resistance was significantly lower (p < 0.05) in group I (0.59 +/- 0.05 mm Hg.mL-1.min-1) than that in group II (1.04 +/- 0.14 mm Hg.mL-1.min-1), and the end-diastolic graft flow/mean graft flow ratio was 1.56 +/- 0.05 in group I and 1.28 +/- 0.04 in group II (p < 0.01). The plasma norepinephrine concentration in group I (223 +/- 52 pg/mL) was significantly low (p < 0.05) compared with that in group II (328 +/- 39 pg/mL) after denervation. Thus, cardiac denervation may have a beneficial effect on systemic hemodynamics and coronary circulation.

Coronary Angiography↗
PubMed1980

Effects of denervation on the composition and synthesis of sarcolemmal proteins.

In vitro synthesis of proteins and changes in polypeptide composition of sarcolemma were studied in innervated and denervated extensor digitorum longus muscle of the rat. A technique of evacuating myoplasm from muscle slices was used as a preliminary step in the preparation of three membrane fractions, M, H and S, containing sarcolemma. On the basis of findings from the previous study and the present investigation, it was concluded that the M fraction was most enriched with extrajunctional sarcolemma. In vitro incorporation of [3H]leucine into membrane proteins of the M fraction showed an apparent linear increase in the rate of protein synthesis from 1-10 days after denervation. The relative increase at 10 days was 137% greater than that of innervated controls. Fractions H and S showed a smaller relative increase. Polypeptide composition of M, H and S fractions based on SDS gel electrophoresis of innervated and denervated muscle, showed qualitative and quantitative changes. The most striking difference was a nominal 29 000 component in M that constituted a disproportionately large peak. Following 10 days of denervation the M fraction underwent significant compositional changes in its electrophoretic profile, the most dramatic of which was a large reduction in the proportion of the 19 000 component. The denervation-induced compositional change is discussed in light of known alterations in the chloride conductance of the muscle plasmalemma.

Animals↗
PubMed1982

Accelerated degradation of junctional acetylcholine receptor-alpha-bungarotoxin complexes in denervated rat diaphragm.

[125] alpha-bungarotoxin was administered to rats in vivo to label acetylcholine receptor in innervated diaphragm, 5-day denervated diaphragm, or diaphragm which had been denervated immediately before labeling. The rate of degradation of junctional toxin-receptor complexes was followed by sacrificing animals at various times after labeling. The rate of degradation of junctional toxin-receptor complexes was significantly faster in 5-day denervated left hemidiaphragm (t 1/2=2.0 days) than in innervated left hemidiaphragm (t 1/2=10.7 days). The rate of degradation of junctional toxin-receptor complexes in left hemidiaphragm denervated at the time of labeling was essentially identical to that in innervated muscle for 3 days but then increased to a significantly more rapid rate (t 1/2=3.7 days in the period 3.13 days after denervation and labelling). These findings support the concept that continuous innervation is needed to maintain the metabolic stability of junctional acetylcholine receptors.

Animals↗
PubMed1983

Lectin receptors in the cockroach neuromuscular system. II. Effects of denervation on muscle lectin receptors.

The binding of fluorescent derivatives of plant lectins to the 6 coxal depressor muscles in the leg of the cockroach was examined at 1, 2, 3 and 5 weeks after denervation. Histochemical analysis of the binding of the lectins to frozen sections of the muscles demonstrated that all detectable binding was to the surfaces of the muscle fibers. In addition, within one week of denervation those muscles which in the innervated state have different amounts of D-galactose and/or alpha-N-acetylgalactosamine on their surfaces, now all have identical amounts of these carbohydrates. Biochemical analysis of concanavalin A and wheat germ agglutinin glycoprotein receptors by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated that approximately 17% of all the receptors detected altered their relative levels in denervated muscles. These changes were observed in those receptors that were present in equal amounts in each of the muscles as well as in those receptors that were distributed among the 6 muscles in a manner that correlated with innervation by an identified motor neuron. However, in spite of these changes that reduced the biochemical differences in the denervated CDMs it was still possible to distinguish among the 6 muscles by the nature of the Con A and WGA glycoprotein receptors. Denervated muscles still present biochemically different cell surfaces to regenerating motor neurons.

Animals↗
PubMed1986

Sinoaortic denervation does not prevent differential Pavlovian conditioning of bradycardia in rabbits.

Recent findings suggest that descending projections from the amygdaloid central nucleus (ACE) to the nucleus of the solitary tract (NTS) may modulate the baroreceptor reflex and thereby facilitate the expression of the bradycardiac conditioned response (CR) in rabbits. The purpose of the present study was to examine the role of the afferent limb of the baroreceptor reflex in differential Pavlovian conditioning of bradycardia in rabbits. Animals received either aortic denervation, sinoaortic denervation or sham denervation. After recovery from surgery, animals received one differential Pavlovian conditioning session per day over the next 6 days. Sinoaortic denervation abolished the baroreceptor reflex as assessed by intravenous injections of phenylephrine. In addition, sinoaortic denervation increased baseline heart rate (HR), altered the topography of the HR unconditioned response, but did not abolish the HR orienting response or prevent the acquisition of bradycardiac CRs. The findings of the present study suggest that afferent barosensory input is necessary for the expression of the HR CR in rabbits. However, descending ACE projections may still play a role in the HR CR by directly affecting NTS neurons.

Amygdala↗
PubMed1988

Effect of unilateral renal denervation on bilateral renal response to saline loading in anteroventral third ventricle-lesioned rats.

Our previous experiments demonstrated that lesions in the anteroventral third ventricle (AV3V) region of the brain attenuated natriuretic and diuretic response to saline loading in rats. To further assess if renal nerves are involved in this impaired response, we compared the effect of acute unilateral renal denervation on the response to saline loading in AV3V-lesioned and intact rats. Rats with electrolytic ablation in the AV3V region were prepared 4 weeks prior to experiments. The arterial blood pressure (BP) and bilateral renal responses to acute expansion of plasma volume by saline loading (0.388 ml/min for 1 h) were measured in rats under pentobarbital anesthesia. Saline loading before renal denervation induced a smaller increase in bilateral renal excretion of sodium and water in AV3V-lesioned rats than in control rats. Acute renal denervation produced ipsilateral natriuresis and diuresis without causing significant change in the excretory functions of the contralateral kidneys in both the lesioned and the control rats. BP and glomerular filtration rate of both groups of rats remained unaltered. The denervation-induced natriuretic and diuretic responses in the lesioned rats were not significantly different from those of the control rats. Subsequent saline loading increased bilateral renal excretion of sodium and water in both groups of rats. However, the previously observed attenuation of natriuretic and diuretic responses to saline loading in rats with AV3V lesions was abolished after renal denervation. These results suggest that the integrity of the AV3V region is necessary for normal regulation of sodium and water balance. Furthermore, there is a functional connection between the renal nerve and the AV3V region in modulating renal excretion during volume expansion.

Animals↗