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The effect of succinylcholine on denervated skeletal muscle.

Succinylcholine, commonly used in anesthesia, paralyzes normal skeletal muscles by blocking transmission at the myoneural junction, but in denervated muscle, it produces sustained muscle contractions lasting several minutes. This denervation hypersensitivity, believed to be due to the progressive enlargement of the receptor area, begins within 2 to 3 weeks and may last for months. Three patients with denervation hypersensitivity were studied: one with isolated denervation of the flexor pollicis longus and two with combined median and ulnar nerve palsy. Within 1 to 2 minutes after administration of succinylcholine, sustained contraction of the denervated muscles occurred and lasted 4 to 5 minutes. Succinylcholine, due to its ability to produce sustained muscle contraction in denervated muscles, may be a useful diagnostic aid in distinguishing loss of function due to nerve injury from tendon disruption.

Adult↗

Hepatic denervation ameliorates sodium and water retention in experimental cirrhosis in rats.

Increased activity in the hepatic sympathetic nervous system may exacerbate salt and water retention in patients with liver cirrhosis. The aim of this study was to evaluate sodium and water homeostasis in rats with cirrhosis induced by diethylnitrosamine and to investigate the influence of hepatic denervation in this model. Animals were randomized into three groups: diethylnitrosamine-treated rats with (N = 13) and without (N = 8) hepatic denervation and control rats (N = 8). Rats were fed a normal salt diet (0.23% sodium ad libitum). The 24-hr measurements for sodium balance, water balance, and creatinine clearance were performed every two weeks for 12 weeks after surgery. Diethylnitrosamine-induced cirrhosis was confirmed histologically. The cumulative change in sodium balance in the innervated diethylnitrosamine-treated rat increased progressively and was significantly higher than the control during the last four weeks of the study. Meanwhile, rats with hepatic denervation showed significantly smaller changes in cumulative sodium balance at week 12 than those in the innervated group. The cumulative changes in water balance in the innervated group were significantly greater at weeks 10 and 12 than those of the denervated and control group, which remained unchanged throughout the study. Creatinine clearance in the innervated group decreased at weeks 10 and 12 by approximately 70% from baseline (P < 0.05); in contrast, it did not change significantly in the denervated group and control group throughout the study. These results demonstrated that hepatic denervation ameliorates sodium and water retention as well as glomerular function in cirrhosis model in rats.

Animals↗

Apoptosis in regenerating and denervated, nonregenerating urodele forelimbs.

Denervated limbs of larval salamanders fail to regenerate if amputated and, unlike adult limbs, undergo regression. The cellular basis of the tissue loss is poorly understood. We used TUNEL staining of larval axolotl limbs fixed and sectioned at intervals after bilateral amputation and unilateral denervation to investigate the role of apoptosis during normal limb regeneration and denervated limb regression. In the first week after amputation a small percentage of apoptotic cells was found in both innervated and denervated limbs. During the second week the apoptotic index remained low in the mitotically active mesenchymal cells of the regenerating limbs, but increased twofold in the nondividing, dedifferentiated cells of the regressing limbs. TUNEL-positive cells resembling apoptotic bodies were restricted primarily to the dedifferentiated area beneath the wound epithelium, but were also present within the wound epithelium itself. Macrophages were identified immunohistochemically and were also found in increased numbers in distal areas of the denervated regressing limbs. The results suggest a role for apoptosis in the early phase of normal regeneration and indicate that denervated limb regression involves an increased rate of apoptosis and removal of apoptotic bodies by macrophages and the wound epithelium.

Animals↗

Standing up with denervated muscles in humans using functional electrical stimulation.

The use of electrical stimulation for denervated muscles is still considered to be a controversial issue by many rehabilitation facilities and medical professionals because prior clinical experience has shown that treating denervated muscle tissue using exponential current over a long time period constitutes an impossible task. Despite this fact, we managed to evoke tetanic contractions in denervated muscle using a long duration stimulation with anatomically shaped electrodes and sufficiently high amplitudes. The pulse amplitudes, which were being used for this purpose, exceeded by far the MED-GV and EC regulations (300 mJ/impulse). For this reason, an application has recently been submitted to have the EC regulations changed accordingly. It takes a tetanic contraction to achieve the desired muscle fiber tension, constituting a hypertrophic stimulus. It is also an appropriate means of exercise, which is capable of creating the metabolic and structural conditions needed (e.g, increased mitochondrial volume and capillary density) to obtain satisfactory muscle performance. With patients suffering from a complete spinal cord injury at level D12/L1, having motor and sensory loss in both lower extremities, we were able to train denervated muscle using long-duration stimulation, evoking single muscle contractions at first, soon followed by tetanic contractions against gravity. To increase the efficacy of this functional electrical stimulation (FES) strengthening program, we used ankle weights. With daily FES training over a period of 1-2 years, denervated muscle was exercised until it produced torques between 16 and 38 Nm in the m. quadriceps. With that muscle force, it is possible to stand up from a sitting position in parallel bars. Our results show that denervated muscle in humans is indeed trainable and can perform functional activities with FES. Furthermore, this method of stimulation can assist in decubitus prevention and significantly improve the mobility of paraplegics.

Capillaries↗

Late denervation in patients with antecedent paralytic poliomyelitis.

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls. The age at the time of acute poliomyelitis, severity of poliomyelitis, residual disability, number of years since acute poliomyelitis, and age at the time of study were comparable in the weakening and control groups. Evidence of remote denervation consistent with antecedent poliomyelitis was demonstrated in all patients by electromyography or muscle biopsy or both. In addition, active denervation (as evidenced by spontaneous activity on conventional electromyography, increased jitter on single-fiber electromyography, or atrophic myofibers) was found in 12 patients in the weakening group and in all 5 controls. Immunohistochemical detection of myofibers expressing the neural-cell adhesion molecule corroborated ongoing denervation in both patient groups. When muscle data from both groups were pooled, correlations were observed between the extent of past reinnervation and the degree of ongoing motor-unit instability. We conclude that the extensive reinnervation of denervated muscle that occurs in paralytic poliomyelitis may be followed by late denervation of the previously reinnervated muscle fibers. Electromyographic and muscle-biopsy evidence of ongoing denervation does not distinguish between stable patients with prior paralytic poliomyelitis and those with new weakness.

Adult↗

Reperfusion arrhythmias after chronic regional denervation of the ischaemic myocardium in pigs.

OBJECTIVE: The aim was to assess the effects of chronic regional denervation of the ischaemic myocardium on reperfusion arrhythmias in a model with sparse coronary collateral circulation. METHODS: Baseline ventricular refractoriness and epicardial activation times were measured together with reperfusion arrhythmias after 15 min (I-15') or 30 min (I-30') of left anterior descending coronary artery occlusion in 38 barbiturate anaesthetised open chest pigs. Twenty pigs (11 in I-15' and nine in I-30') had a chronic (two week) denervation of the left anteroseptal region, whereas 18 pigs (10 in I-15' and eight in I-30') were sham operated (non-denervated) controls. Denervation was induced by pericoronary application of phenol and verified by absence of adrenergic histofluorescence. RESULTS: As compared with controls, denervated pigs showed: (1) longer activation times: 20.3 (SD 5.2) ms v 16.5 (4.6) ms, p < 0.001; (2) slightly longer refractory periods: 348(28) ms v 334(27) ms; (3) a tendency to lower postreperfusion ectopic activity: ectopic beats divided by time free of ventricular tachycardia: 0.13(0.19) v 0.34(0.40) in I-15', and 0.21(0.24) v 0.39(0.44) in I-30'; (4) slower ventricular tachycardia in I-30': 140(29) beats.min-1 v 185(29) beats.min-1, p < 0.009; and (5) comparable incidence of postreperfusion ventricular fibrillation: 4/11 pigs v 2/10 in I-15', and 5/9 v 4/8 in I-30'. CONCLUSIONS: Selective chronic denervation of the ischaemic myocardium was unable to protect against malignant reperfusion arrhythmias in hearts with human-like coronary collaterals. This was confirmed at two ischaemic periods known to produce progressive catecholamine accumulation and increased adrenoceptor density in the ischaemic myocardium.

Animals↗

Long-term denervation of the humerus in turkeys as an experimental model for osteopenia.

The aim of this study was to evaluate the influence of long-term denervation on volumetric bone mineral density, and geometrical and mechanical properties of the humerus in turkeys. The experiment was conducted from d 22 after hatching until wk 17 of life. All experimental birds (male turkeys) were randomly divided into 2 weight-matched groups. The first group of turkeys served as the control group and underwent a sham operation on the right wing, and the second group was subjected to surgical denervation of the right humerus. The denervation was performed by neurectomy of the radialis and the mediano-ulnaris nerves in the region of the proximal epiphysis of the humerus. All the left wings within both groups were surgically untouched. The left humerus served as the control bone to the right humerus in both investigated groups. Effect of denervation of humerus was determined in terms of geometrical and mechanical properties and quantitative computed tomography. The denervation of the humerus in turkeys significantly decreased volumetric bone mineral density, and geometrical and mechanical properties of this bone, when compared with the results obtained in humerus from the sham-operated or surgically untouched wings. However, no significant differences between right and left humerus were observed when analyzing all of the investigated parameters in the sham-operated group of turkeys. It is concluded that long-term denervation of humerus in turkeys induces osteopenia and may serve as a new experimental model for investigating factors that affect skeletal homeostasis in poultry and other vertebrates.

Animals↗

Effects of sinoaortic baroreceptor denervation on blood pressure and PNMT activity in medulla oblongata and spinal cord of normotensive and genetically hypertensive rats.

The effects of sinoaortic denervation on arterial blood pressure and central activity of phenylethanolamine-N-methyl transferase (PNMT, the last enzyme in adrenaline biosynthesis), were compared in normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHR-SP). Denervation of the arterial baroreceptors caused immediate increases in mean arterial blood pressure (MAP) in all three strains which were maximal at 90 min (32 mmHg in WKY, 51 mmHg in SHR and 80 mmHg in SHR-SP). Spinal cord PNMT activity increased above sham-operated levels in WKY at 90 min, but PNMT levels in SHR and SHR-SP, already significantly higher than in WKY, were not altered acutely after sinoaortic denervation. Over a seven day period after baroreceptor denervation, MAP rose by 15 mmHg in WKY and PNMT activity was about 100% greater in spinal cord and ventral medulla. In the two genetically hypertensive strains sinoaortic denervation failed to produce a further sustained rise in pressure or and PNMT activity in the ventral medulla or spinal cord. We suggest that increased activity of bulbospinal adrenaline neurons contribute to the sustained elevation in pressure seen in intact SHR and SHR-SP, as well as in WKY after denervation of arterial baroreceptors.

Animals↗

Effect of Prior Dopamine Denervation on Survival and Fiber Outgrowth from Intrastriatal Fetal Mesencephalic Grafts.

[3H]Dopamine (DA) uptake radioautography and tyrosine hydroxylase (TH) immunocytochemistry were used to assess quantitatively the effects of the presence or absence of host mesostriatal DA afferents on the survival and fiber outgrowth from fetal ventral mesencephalic DA neurons grafted into the neostriatum of adult recipient rats. Rats received bilateral intrastriatal transplants of fetal ventral mesencephalic tissue 1 month after a unilateral injection of 6-hydroxydopamine (6-OHDA) into the right nigrostriatal bundle (denervated side). Five to six months later, some of the grafted rats received a second 6-OHDA injection in the left nigrostriatal bundle (acutely denervated or 'intact' side). After a further 7 days, slices of each hemisphere from the latter rats were incubated with [3H]DA and processed for film and high resolution radioautography. The density of the film radioautographs was measured with a computerized image analysis system and calibrated by silver grain cluster (i.e. DA terminal) counting over selected areas of the same sections in light microscope radioautographs. The brains of the remaining grafted rats were processed for TH immunoreactivity 6 - 12 months after graft surgery. Neither the size of the grafts, nor the number of surviving TH-positive graft neurons showed any significant difference between the nondenervated and the denervated sides. However, the size of the TH-positive cell bodies was significantly greater in the grafts on the denervated side. In the [3H]DA uptake radioautographs, considerable outgrowth of DA fibers was evident in the neostriatum on the 'intact' side in spite of the presence of an intact host DA innervation until 7 days before sacrifice. The overall DA fiber outgrowth was nevertheless almost two-fold greater on the denervated side, and extended deeper into the host neostriatum than on the 'intact' side; only 7% of the total neostriatal area, on average, was at background level compared to 30% on the 'intact' side, and the overall density of neostriatal DA innervation amounted to 36% of normal as compared to 20% on the 'intact' side. The correlation between the overall density of graft-derived DA innervation and the size of the grafts was linear on the 'intact' side, but reached a plateau with relatively small grafts on the denervated side. However, the ventral striatum on both sides was very poorly innervated by these grafts. These findings demonstrate that the mature neostriatal tissue can support axonal growth and innervation from grafted fetal DA neurons even in the presence of a normal complement of endogenous DA fibers. Prior removal of the host striatal DA innervation does not influence the overall size of the grafts nor the number of surviving DA neurons, but induces an increase in the cell body size and fiber outgrowth of the grafted DA neurons.

Journal Article↗

Effect of sympathetic denervation on the relaxing responses of rabbit arterial smooth muscle.

1. The present study reports on the influence of chemical denervation by 6-hydroxydopamine (6-OHDA) on the relaxing responses to carbachol, sodium nitroprusside, zaprinast, adenosine, forskolin and 3-isobutyl-1-methylxanthine (IBMX) of ring preparations of rabbit renal and femoral arteries. 2. Carbachol was found to induce a complete abolition of the tone induced by 5-hydroxytryptamine (0.1-1.0 microM), both in the renal and the femoral arteries. The profile of the carbachol-induced relaxation in both the renal and femoral arteries obtained from 6-OHDA-treated rabbits was similar to that observed in control animals; relaxing responses obtained with some of the concentrations of carbachol were, however, found to be greater (P < 0.01) in denervated arteries. Sodium nitroprusside was also found to be an effective relaxant agent in both renal and femoral arteries, though more potent in the former but was unaffected by denervation. Zaprinast relaxed both renal and femoral artery ring preparations, and again, no significant difference was observed between control and denervated animals. 3. The cyclic AMP-mediated relaxing responses to adenosine, forskolin and IBMX were found to be similar in renal and femoral arteries of control arteries, producing almost complete abolition of pre-existing tone. The adenosine- and IBMX-induced relaxing responses in renal and femoral arteries were found to be similar in control and denervated animals. However, the concentration-response curve to forskolin was shifted to the left by 2.5 and 1.5 log units in preparations of renal and femoral arteries of denervated rabbits, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Effects of brocresine (NSD-1055) and cycloheximide on amino acid decarboxylase activities in gastric mucosa of normal and vagally denervated rats.

1. Histidine decarboxylase activity of rat stomach fluctuates depending upon the functional state of the stomach. This varying enzyme activity poses special problems in assessing the effectiveness of enzyme inhibitors. After vagal denervation gastric histidine decarboxylase is markedly activated and remains at a high, stable level, which is unaffected by the functional state of the stomach. Thus it appears that vagally denervated rats are well suited for studies on histidine decarboxylase inhibitors.2. In vivo, brocresine (NSD-1055) was found to be a more effective inhibitor of gastric DOPA decarboxylase than of gastric histidine decarboxylase. With the fairly high dose given (200 mg/kg) the inhibition of histidine decarboxylase was at most 75-85% and quite short-lasting. The DOPA decarboxylase activity, which was not affected by vagal denervation, was inhibited more than 95% by brocresine; this inhibition was longer-lasting.3. Cycloheximide, which probably lowers gastric histidine decarboxylase activity by inhibiting enzyme synthesis, was maximally effective at a dose level as low as 1 mg/kg. Gastric DOPA decarboxylase was not inhibited by cycloheximide. Vagotomized rats and control rats responded similarly.4. Combined treatment of vagally denervated rats with brocresine and cycloheximide resulted in a rapid and persistent reduction of the histidine decarboxylase activity. It is concluded that the failure of brocresine alone to induce a lasting inhibition of histidine decarboxylase is due to continuous, rapid synthesis of new enzyme.5. The calculated half-life of gastric histidine decarboxylase was 75 min in vagally denervated rats and 45 min in normal fasted rats. The results suggest that the increased enzyme activity after vagal denervation is caused by an increased rate of enzyme synthesis.

Animals↗

Effects of the chemical denervation on the glial cells of the rat pineal gland: an immunocytochemical study during postnatal development.

We have studied the postnatal evolution of the glial cells in the rat pineal gland after its chemical pre- and perinatal denervation, by the assessment of the immunocytochemical expression of three antigens characteristic of glial cells i.e., vimentin (VIM), glial fibrillary acidic protein (GFAP), and S-100 protein. The neurotoxic agents we applied consisted of 6-hydroxydopamine (6-OHDA) administered during the first 5 postnatal days, and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) injected to pregnant rats in the 15th gestational day. VIM immunoreactivity was detected in pineal glial cells from the first postnatal day, both in denervated and control groups. However, in denervated glands, the maturation process of the glial cells is considerably accelerated, since they appear completely detached of the connective tissue septa at day 15. From day 30, the number of VIM-positive structures progressively increases until adulthood, when a large number of immunoreactive cell processes produces a reticular appearance to the denervated pineal gland. The first GFAP and S-100 protein immunoreactive cells were observed earlier in denervated animals (5th postnatal day for S-100 protein, and 10th postnatal day for GFAP) compared with controls. In the experimentally denervated groups, the population of positive cells, as well as their size and the number of their cell processes, is considerably higher and progressively increased. They were always characteristically located in the proximal half of the gland. From day 45, this region of the gland shows a notable amount of hypertrophic positive cells with thick processes, showing a gliotic aspect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin.

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In experiment 1, one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice that were then infused for 13 days with PBS or 10 microg leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague-Dawley rats that were infused with 50 microg leptin/day. Leptin had little effect on EPI weight or norepinephrine (NE) content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.

Adipose Tissue↗

Hypoxemia and low Crs in vagally denervated lambs result from reduced lung volume and not pulmonary edema.

Vagal denervation performed in the intrathoracic region in newborn lambs leads to hypoxemia and decreased respiratory system compliance (Crs), which could result from atelectasis and/or pulmonary edema. The objective of the present study was to quantify the relative roles of alveolar derecruitment and pulmonary edema as underlying cause(s) of respiratory failure. Vagal denervation was performed in the intrathoracic region and below the recurrent laryngeal nerves in six newborn lambs within 24 h of birth, whereas six were sham operated. Pre- and postinflation Crs was measured to investigate the presence of alveolar derecruitment. Pulmonary edema was assessed with lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage. Compared with that in the sham-operated animals, Crs was significantly lower in vagally denervated animals. However, postinflation, pulmonary system compliance obtained by quasi-static lung inflation and deflation to 30 cmH2O showed no significant difference between the sham-operated and denervated lambs. The lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage were similar in denervated and sham-operated groups. We provide evidence that reduced lung volume and not pulmonary edema is associated with intrathoracic vagal denervation and is the likely underlying mechanism for hypoxemia and low Crs.

Afferent Pathways↗

Selective microsurgical sympathetic denervation of the rat pancreas.

Autonomic nerves have been implicated in the regulation of endocrine and exocrine pancreatic secretion. The purpose of the present study was, therefore, to develop a simple, reproducible technique for selective sympathetic denervation of the rat pancreas. Under ether anesthesia a midline laparotomy was performed, the pancreas and spleen were freed from adhesions. The peritoneum was incised over the superior and inferior pancreaticoduodenal arteries and the splenic artery at their origin. The incised areas were stained with 1% toluidine blue solution. The pancreaticoduodenal and splenic nerves were visualized and resected. 1, 2 and 3 weeks after the denervation procedure the norepinephrine (NE) content of the pancreatic tissue was determined. Cholinergic and nitric oxide synthetase (NOS)-immunoreactive nerve structures were identified by immunohistochemistry 1 week after denervation. In denervated tissue the NE content after 1 week was 98% lower than measured in controls. With time, there was a gradual increase of the NE content, although it reached only 25% of the values measured in sham-operated animals at 3 weeks. There was no concomitant denervation of the duodenum. Cholinergic and NOS nerve structures were still present 1 week after denervation.

Animals↗

Adverse effects of chronic cardiac denervation in conscious dogs with myocardial ischemia.

The extent to which total chronic cardiac denervation protects the ischemic myocardium was investigated in conscious dogs. The major hemodynamic difference after coronary artery occlusion was that left ventricular end-diastolic pressure rose significantly more, P less than 0.01, in the denervated group (12 +/- 1.5 mm Hg) than in the normal group (4.4 +/- 1.4 mm Hg). Blood flow (radioactive microspheres) in the ischemic endo- and epicardium fell to similar levels at 3-5 minutes after coronary occlusion, but was significantly less (P less than 0.01) in denervated dogs at 3 hours after occlusion in the endo- (0.05 +/- 0.01) and epicardium (0.30 +/- 0.02 ml/min per g), than in the endo- (0.13 +/- 0.03) and epicardium (0.42 +/- 0.05 ml/min per g) in the normal group. A subgroup of normal dogs was also studied, with left ventricular end-diastolic pressure increased by volume loading to levels similar to those observed in the denervated group after coronary occlusion; in these dogs, blood flow was similar to that in the other two groups 3-5 minutes after coronary artery occlusion, but, at 3 hours, was significantly more depressed (P less than 0.01) than that observed in normal dogs without volume loading in both endo- (0.03 +/- 0.01) and epicardial (0.25 +/- 0.03 ml/min per g) layers. Infarct size, as a fraction of the area at risk, was significantly greater (P less than 0.05) in the denervated group (60 +/- 4.3%) and in the subgroup of normal dogs with elevated left ventricular end-diastolic pressure (73 +/- 5.8%), compared with the normal group without volume loading (37 +/- 8.1%). Thus, in conscious dogs, total chronic cardiac denervation exerts an adverse effect on infarct size which may be related to the sustained elevation in left ventricular end-diastolic pressure and consequent impairment of collateral perfusion.

Animals↗

Effects on the urinary bladder and urethra of different pharmacological treatments. An in-vivo study in normal and parasympathetically denervated cats.

The difference in autonomic nerve functions in vivo between the neurologically normal and the long-term parasympathetically denervated feline bladder and urethra was studied. For this purpose the vesical and urethral responses to electrical hypogastric and pelvic nerve stimulations and to various autonomic stimulating agents were investigated into. The nature of these responses was explored by different blocking agents. In the normal feline bladder phenylephrine caused a contraction. Noradrenaline always resulted in a bladder relaxation which was changed into a contraction after beta-adrenergic blockade. In the parasympathetically denervated bladders noradrenaline caused in most cats a bladder contraction without previous beta-adrenergic blockade. In the normal bladders hypogastric nerve stimulation always evoked an initial contraction and a subsequent bladder relaxation. In the parasympathetically denervated bladders, however, a novel response of a sustained bladder contraction was achieved. This contraction was blocked by a ganglionic or an alpha-adrenergic blocking agent, indicating that the reaction was mediated in preganglionic cholinergic fibres via postganglionic adrenergic neurons. The results indicat that parasympathetic denervation induces a change in the adrenergic receptor functions of the urinary bladder. Thus, in the neurologically normal bladder beta-adrenergic receptors mediating relaxation are in predominance while after long-term parasympathetic denervation alpha-adrenergic receptors mediating contraction dominate. No change in adrenergic receptor function was demonstrated in the urethra. alpha-Receptors mediating contraction were found to predominate both before and after parasympathetic denervation.

Acetylcholine↗

[Experimental studies on sympathetic innervation of lower urinary tract. Quantitation of nerve terminals and urethral pressure response after hypogastric denervation].

On 6 female mongrel dogs (denervated group), bilateral hypogastric nerves were cut distally to the inferior mesenteric ganglion. Five dogs were kept intact as a control group. After 2-5 months, urethral pressure response to continuous noradrenaline infusion (0.1 microgram/kg/min) was monitored. The urethral pressure rose significantly after noradrenaline loading in each group, however there was no significant difference in the degree of the response between the denervated group and control group. Subsequently, the bladder and the urethra were extirpated to determine the intrinsic noradrenaline content. The tissue noradrenaline concentration was highest in the posterior urethra, intermediate in the bladder base and lowest in the bladder dome. Although these values tended to be lower in the denervated group than in the control group, no significant difference was obtained between the groups in each portion. These results suggest that the majority of sympathetic components which consists in the hypogastric nerve may involve short adrenergic neurons. Thus, chronic hypogastric denervation alone does not induce sympathetic denervation supersensitivity. Simultaneous decentralization of the pelvic nerve may be necessary for inducing sympathetic denervation supersensitivity.

Animals↗