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[Jejunal myenteric denervation induced by benzalkonium chloride].

The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

Animals↗

Increased active stress generation of denervated rat intestinal smooth muscle: functional analysis of muscarinic receptor population.

The effects of denervation on the active stress production by the longitudinal muscle (LM) layer of rat jejunum were examined. Extrinsic and myenteric denervation of a segment of rat jejunum was accomplished by the serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). Isolated muscle contraction experiments revealed that the LM of the jejunum taken from rats treated with BAC 15 days before developed significantly increased active stress in response to bethanechol and carbachol, but not in response to potassium chloride. No change in -log EC50 values of any of the agonists was observed in the denervated LM layer, although a significant increase in the slope of the carbachol and bethanechol concentration-response curves was observed in the denervated LM. Schild analysis of several muscarinic antagonists revealed a 3-fold increase in the apparent dissociation constant of the M2 antagonist methoctramine in BAC-treated LM. These results suggest that the increased responsiveness of the denervated LM may originate in the muscarinic receptor population of the myocytes.

Animals↗

[The increase in endocytosis of mouse skeletal muscle after denervation and the proliferation of satellite cells].

The relationship between increase of endocytosis and proliferation of satellite cells in mouse skeletal muscle was studied by biochemical and culture methods in vitro. The results indicated that: (1) 4 d or 6 d after denervation, increase of endocytosis and proliferation of satellite cells in denervated muscle were induced. (2) Actinomycin D inhibited activation of satellite cells and endocytosis in normal muscle. (3) While in denervated muscle, actinomycin D inhibited proliferation of satellite cells as well as increase of endocytosis, but could not prevent muscle atrophy after denervation. These results imply that proliferation of satellite cells and increase of endocytosis in the muscle may concur to the appearance of some factors after denervation, or increase in endocytosis is a mere result of proliferation of satellite cells.

Animals↗

Modulation of IGF mRNA abundance during muscle denervation atrophy.

Changes in skeletal muscle activity cause dramatic alterations in muscle mass. Increased load on a muscle (synergistic overload) results in muscle hypertrophy. During hypertrophy, skeletal muscle concentrations of insulin-like growth factors (IGF-I and IGF-II) mRNAs increase. To clarify the role of IGFs in regulating muscle mass, this study examined whether IGF-I and -II mRNA levels were altered during decreased muscle activity (denervation). Gastrocnemius weights decreased 4.2%, 7.7%, 18.1%, 27.7%, 35.1%, 45.0%, and 60.3% at 2, 3, 5, 7, 10, 12, and 17 d following denervation, respectively. Muscle DNA content remained constant throughout the first 12 d after surgery, but increased above control levels at day 17. During the first week after surgery, gastrocnemius IGF-II mRNA remained constant. However, IGF-II mRNA abundance was 2.5-fold greater than controls by 10 d of denervation, 3-fold by 12 d, and 6.8-fold by 17 d. On the other hand, IGF-I mRNA levels were not affected by denervation. In conclusion, although increased muscle activity results in a change of IGF-I mRNA expression, decreased muscle activity has no effect on IGF-I mRNA expression. In contrast, IGF-II mRNA levels increase with long-term denervation as well as with increased muscle activity. This study suggests that muscle activity may not be the only factor affecting IGF-I and -II expression.

Animals↗

[Absence of the effect of nitric oxide on pulmonary and systemic hypertension induced by sino-aortic denervation].

Inhaled nitric oxide, a selective pulmonary vasodilator, reverses hypoxic pulmonary vasoconstriction and is an effective treatment in some cases of human pulmonary hypertension. Localization of nitric oxide synthase had indicated a neural role for nitric oxide. Thus, we studied the interactions between inhaled nitric oxide and systemic and pulmonary vascular reactivity in acute neurogenic hypertension. In 6 male beagle dogs (mean weight: 15 +/- 1 kg), anesthetized by chloralose (8 cg/kg) and in spontaneous ventilation, the hemodynamic effects on systemic and pulmonary circulation of inhaled nitric oxide (12 ppm) were studied before and after acute sino-aortic denervation. The hemodynamic effects of intravenous propranolol (300 micrograms/kg) were studied after denervation. Mean arterial pressure (MAP), pulmonary capillary pressure (PCP), mean arterial pulmonary pressure (MAPP), cardiac input (CI) and oxygen venous saturation (SvO2) were measured. [table: see text] Sino-aortic denervation causes an acute and transitory pulmonary hypertension due to a double mechanism: a post-capillary hypertension (increase PCP) secondary to an increase left ventricular post-charge by systemic hypertension and a precapillary hypertension. In fact, vascular pulmonary resistances increase from 1.8 +/- 0.1 to 3.4 +/- 0.8 uW after denervation (p < 0.05). Change in pulmonary vascular reactivity induced by catecholamines is probably involved. Propranolol but not inhaled nitric oxide reverse pulmonary hypertension due to sino-aortic denervation.

Administration, Inhalation↗

Type-specific changes in fibre size and satellite cell activation following muscle denervation in two strains of turkey (Meleagris gallopavo).

Morphological features and the chronology of muscle changes after denervation were studied over a 21 d period in 2 heavy (HW) and light-weight (LW) strains of 6-wk-old male turkeys. The atrophy of tibialis cranialis, gastrocnemius lateralis and plantaris muscles was apparent at d 3 after denervation. By d 21 the weight of these muscles had reached 45-60% of that of nondenervated contralateral muscle. Cellular lesions, such as irregularities in mitochondrial distribution or coagulative necrosis with fragmentation and lysis associated with moderate infiltration of inflammatory cells, were similar in both strains. Ten days after denervation, immunolabelling of a proliferating cell nuclear antigen (PCNA) expressed during the G1 and S phase of the cell cycle revealed satellite cell activation in denervated muscles. The number of satellite cells activated at d 21 was markedly greater in the HW than LW strain. Morphometric analysis revealed that fast twitch (type II) fibres were atrophied after denervation, whereas slow-twitch (type I) and slow tonic (type III) fibres were hypertrophied from d 10. Hypertrophy occurred more rapidly in the LW than HW strain.

Animals↗

Tenascin in denervated human muscle.

Tenascin is a large oligomeric glycoprotein of the extracellular matrix. Its location is innervated muscle tissues. We investigated immunohistologically, using two monoclonal antibodies (mah) against Tenascin, biopsied denervated human muscle of children and adults. Tenascin was present in the interstitial space among denervated muscle fibres. Accumulation of Tenascin in denervated adult muscle tissue was frequent, accumulation in denervated muscle tissue of children was sparse and weak. The two antibodies reacted correspondingly. Tenascin was not only found in the vicinity of atrophic muscle fibres, but also close to normally sized fibres, suggesting an early stage of denervation even before reduction of muscle fibre volume.

Adult↗

MR of denervated tongue: temporal changes after radical neck dissection.

PURPOSE: The purpose of this study was to evaluate the temporal changes of MR imaging in the denervated tongue after a radical neck dissection. METHODS: One hundred seventy-four consecutive MR studies in 116 patients with radical neck dissections for malignant tumors of the head and neck were evaluated retrospectively. Patients with tumors involving the tongue or hypoglossal nerve were not included in this study. RESULTS: Abnormal signal intensity and/or hemiatrophy on the side of the tongue operated on was seen in 22 patients who had hypoglossal paralysis after radical neck dissection. The denervated side of the tongue appeared hypointense to hyperintense relative to the normal side on T1-weighted images and hyperintense on T2-weighted images. Signal intensity ratios of the abnormal to normal muscles were 0.9-1.6 on T1-weighted images and 1.3-2.8 on T2-weighted images. High signal intensity on T1-weighted images appeared 5 months or more after the dissection, whereas on T2-weighted images, the most prominent increases in signal intensity appeared in the first several months after denervation. Hemiatrophy of the tongue was observed on MR images obtained more than 6 months after surgery. CONCLUSION: MR findings in the denervated tongue are compatible with histologic changes and are characterized by an enlarged extracellular fluid space or fatty infiltration. The pattern of signal intensity and the degree of hemiatrophy suggest the duration of denervation.

Adult↗

[Ultrastructural morphometric study of the prostate of the rat after microsurgical denervation].

OBJECTIVE: To analyze the effects of rat prostate denervation on the ultrastructure of this gland. MATERIAL AND METHODS: Eighty Sprague-Dawley rats (300-350 g. weight) were studied. Forty-two were anesthetized and right major pelvic ganglion (MPG) excised. After 28-30 days, same size prostatic ventral lobe (VL) was obtained for transmission electron microscopy (TEM) study and computerized image analysis. These results were compared with those from 38 right VLs of same aged, non-operated rats. RESULTS: A significant decrease of supranuclear and cell heights was observed as well as of the area of epithelial cells after denervation (change in cell polarity). A reduction of Golgi apparatus and endoplasmic reticulum areas, and of secretory granules and apical microvilli count (p < 0.001) was also demonstrated in the denervated rats. These findings are consistent with a change of these cells towards a less active phenotype. Stromal smooth muscle cells, on the other hand, showed only an increase of cytoplasmic ribosomal aggregates area. CONCLUSIONS: The present study showed an epithelial atrophy of rat prostate after denervation. Ultrastructural findings also suggest an overall decrease of epithelial cell's secretory activity. Nevertheless, the increase of ribosomal area in stromal smooth muscle cells could reflect their activation after denervation.

Animals↗

Immediate effects of hepatic denervation on hepatic hemodynamics in dogs.

This study was conducted to examine the immediate effects of hepatic surgical denervation on the hepatic blood flow in anesthetized dogs. A surgical denervation model was created by removing all visible nerves around the portal vein, the hepatic artery and the bile duct along with the peri-hepatic tissues. The hepatic hemodynamics were measured pre and postoperatively in the hepatic denervation group (n = 6) and control group (n = 6). The portal venous blood flow and the hepatic tissue blood flow showed no significant differences between the two groups throughout the experiment. The hepatic arterial blood flow at 120 min after denervation (220 +/- 46 ml/min) had significantly higher than that (114 +/- 14 ml/min) in the control group (p < 0.05). These results indicate that hepatic denervation is implicated in the hepatic arterial blood flow, and the hepatic nerves play an important role in the regulation of the hepatic arterial blood flow.

Animals↗

An analysis of the postjunctional component of denervation supersensitivity in the isolated vas deferens of the guinea-pig.

An attempt was made to devise evidences for a role of calcium ions in the postjunctional component of denervation supersensitivity. The evidences obtained are: chronic postganglionic denervation increases sensitivity and maximum response of the vas deferens to cumulative concentrations of calcium and alters the pattern of response to low-calcium, potassium-rich Krebs solution; denervation supersensitivity could not be demonstrated after depolarization, and in KC1-Ringer or in Ca2+/--free Krebs solution the rate of loss of responsiveness to acetylcholine was delayed after denervation whereas the rate of loss of responsiveness to noradrenaline was unaffected. It is suggested that the postjunctional component of denervation supersensitivity in the isolated vas deferens of the guinea-pig is due, at least partially, to an increased availability of a membrane-bound calcium store(s) associated to an enhanced cell membrane permeability to the ion.

Acetylcholine↗

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression.

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

Animals↗

Differential effects of denervation on acetylcholinesterase activity in parasympathetic and sympathetic ganglia of the frog, Rana pipiens.

The transsynaptic regulation of acetylcholinesterase (AChE) was studied by recording the changes in enzymatic activity following denervation in two types of autonomic ganglia in the frog, Rana pipiens. Opposite effects on AChE were found in the parasympathetic cardiac ganglion and in the sympathetic lumbar ganglion; denervation produced a significant increase in AChE activity in cardiac ganglia but a significant decrease in lumbar ganglia. The relative effects of denervation on intracellular and total AChE were examined by selectively inhibiting extracellular AChE with echothiophate, a poorly lipid-soluble cholinesterase inhibitor. Denervation resulted in a significant increase in intracellular AChE in cholinergic cardiac ganglia but had no effect on intracellular AChE activity in adrenergic lumbar ganglia. Histochemical studies revealed little change in extracellular AChE staining upon denervation in the cardiac ganglion, whereas in the lumbar ganglia there was a loss of AChE-specific reaction product. These results raise the possibility that the transsynaptic control of AChE activity by innervation in the frog is influenced by the transmitter synthetic properties of the postsynaptic ganglion cells.

Acetylcholinesterase↗

Force and fatiguability of sprouting motor units in partially denervated rat plantaris.

The contractile properties of single motor units of rat plantaris were measured in situ 7 days following muscle partial denervation, achieved by section of radicular nerve L4. Partially denervated muscles weighed less, generated weaker twitch and tetanic forces, and contained denervated fibers, as evidenced by indirect/direct stimulation force ratios less than 1. Fast motor units (over 90% of unit pool) showed elevated twitch and tetanic responses (222% and 171% of controls, respectively) and elevated twitch-to-tetanic force ratios. Although partial denervation did not alter the mean fatiguability of fast motor units, fewer proportions of units remained in the extreme categories of fatigue resistance, with a clustering of units in the intermediate ranges. Slow units, while showing elevated twitch and tetanic responses, did not change in fatiguability. Glycogen depletion of the fibers of two fast motor units in partially denervated muscles revealed the presence of fibers varying in size, and in staining intensities for succinate dehydrogenase and ATPase, within the same motor unit, as a result of motoneurone sprouting.

Animals↗

Neural regulation of adrenal chromaffin cell function in the mouse--stress effect on the distribution of [3H]dopamine in denervated adrenal medulla.

Effects of adrenal denervation and stress on the distribution of radioactivity in the adrenal medulla after [3H]dopamine injection was studied by light microscopic autoradiography. Denervation of the adrenal gland abolished the stress (restraint plus water immersion) induced degranulation of adrenal chromaffin cells and decreased uptake of [3H]dopamine. Denervated chromaffin cell of stress mice incorporated as high radioactivity as those of no stress mice. Adrenal denervation increased the uptake in adrenaline-storing (A) cells but not in noradrenaline-storing (NA) cells. The characteristic distribution of radioactivity (high radioactivity along the cortico-medullary junction) was reinforced by adrenal denervation. Under stress conditions, increase in pituitary adrenocortical system did not enhance the uptake of [3H]dopamine in chromaffin cell while increase in nerve activity suppressed the uptake. Spontaneous activity of the splanchnic nerve to adrenal chromaffin cells suppresses the uptake of [3H]dopamine. The neural influence is stronger on A cells than on NA cells. Chromaffin cells in the subcortical zone are more intensely controlled by the neural influence than those in the central zone.

Adrenal Medulla↗

Effect of chronic sympathetic denervation on cerebrovascular hypertrophy during the development of hypertension in rats.

The present study was designed to examine the trophic effect of sympathetic nerves on cerebrovascular hypertrophy in developmental hypertension. Unilateral superior cervical ganglionectomy was performed in spontaneously hypertensive rats at 4 weeks of age, and wall-to-lumen ratios of cerebral arteries were determined at 5 weeks, 2 months or 5 months after denervation. To estimate the thickness of the vessel wall, a freeze substitution technique was used for the preparation of cerebral arteries. Basal mean arterial blood pressure measured through cannulated femoral artery was 127 +/- 2, 146 +/- 7 and 168 +/- 6 mm Hg (mean +/- S.E.M.) at 9 weeks, 3 months and 6 months of age, respectively. The wall-to-lumen ratios in the denervated and innervated hemispheres were 0.124 +/- 0.004 and 0.129 +/- 0.005 at 9 weeks, 0.127 +/- 0.003 and 0.169 +/- 0.004 (P less than 0.02 vs denervated) at 3 months, and 0.194 +/- 0.007 and 0.222 +/- 0.006 (P less than 0.05 vs denervated) at 6 months. The effect of denervation was more significant in downstream vessels (diameter less than or equal to 100 microns) than larger ones. We conclude that wall-to-lumen ratio is correlated well with a rise in basal blood pressure, and chronic interruption of the sympathetic nerves attenuates normal occurrence of vascular hypertrophy during the development of hypertension.

Animals↗

Effects of neonatal sympathetic denervation on amylase secretion in the adult rat parotid gland: difference in beta 1- and beta 2-adrenoceptor response.

Changes in amylase secretion and cyclic AMP accumulation in response to various secretagogues were studied in parotid glands of adult rats subjected to neonatal sympathetic denervation by unilateral excision of the superior cervical ganglion. Denervation decreased the gland content of amylase and both basal and the stimulated levels of cyclic AMP were elevated. The secretory cells of neonatally denervated glands exhibited enhanced maximal enzyme discharge in response to beta-adrenoceptor agonists. However, the selective beta 1-agonist, prenalterol was not effective in this respect whereas an enhanced maximal secretory response to the beta 2-selective agonist, terbutaline, was particularly prominent. DBcAMP was also more efficient in inducing amylase release from the denervated gland. The result of the present study demonstrate that the usual dominance of the beta 1-adrenoceptor subtype in eliciting amylase release is lost, implying that the differentiation of the beta-adrenoceptor into its subtypes is altered by neonatal sympathetic denervation.

Amylases↗

Adrenergic and neuropeptide Y supersensitivity in denervated nasal mucosa vasculature of the pig.

The effects of sympathetic denervation for 2 weeks on vasoconstrictor reactivity to alpha-adrenoceptor agonists, neuropeptide Y (NPY) and alpha,beta-methylene adenosine triphosphate (mATP) were investigated in different vascular compartments of the nasal mucosa of pentobarbital-anesthetized pigs. Supersensitivity to the vasoconstrictor actions of noradrenaline (NA) was observed in the function of both resistance vessels (as revealed by a reduction in arterial blood flow) and capacitance vessels (reflected by a reduction in nasal mucosal volume). The NA supersensitivity was, to a large extent, of prejunctional type since inhibition of neuronal uptake by desipramine also markedly enhanced the NA response. Whereas the reduction in arterial blood flow and in mucosal volume induced by the alpha 1-agonist, phenylephrine, was not changed by denervation, the effects of the alpha 2-agonists UK 14.304 and oxymetazoline were enhanced and/or prolonged. Furthermore, the reduction in blood flow and volume induced by NPY was enhanced in both amplitude and duration. The effects of mATP on the amplitude of the volume response and the duration of the blood flow and volume changes were increased. The maximal reduction in superficial blood flow was larger, as revealed by the laser Doppler flowmetry signal, when NPY or adrenoceptor agonists were given to denervated animals. It is concluded that sympathetic denervation is associated with increased sensitivity and prolonged responses to a variety of vasoconstrictor agents in the pig nasal mucosa in vivo. However, alpha 2-adrenoceptor, NPY and mATP mechanisms seem to be influenced more by denervation than by alpha 1-adrenoceptor sensitivity.

Animals↗