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PubMed2003

Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-beta1 in streptozotocin-induced diabetic rats.

In long-term diabetes mellitus, the progression of nephropathy has been related to the occurrence of autonomic neuropathy. This study was designed to evaluate the effects of bilateral denervation of the kidneys of streptozotocin-diabetic rats, an experimental model that presents diabetic nephropathy with increased abundance of cortical GLUT1 in the kidney and increased urinary excretion of albumin and transforming growth factor-beta1 (TGF-beta1). Twenty-four-hour urinary TGF-beta1 (ELISA), urinary albumin (electroimmunoassay) and GLUT1 protein levels (Western blotting) in the renal cortex and medulla were evaluated in diabetic (n=13) and control (n=13) rats 45 days after streptozotocin injection, submitted or not to surgical renal denervation. Evaluations were performed 15 days after the surgery. The effects of renal denervation were confirmed by intra-renal decrease of norepinephrine levels. Mean arterial pressure did not differ between diabetic and control rats, whether they underwent renal denervation or not. Renal denervation increased cortical (6905+/-287, 3506+/-193, 4144+/-246 and 5204+/-516 AU in renal-denervated controls, controls, renal-denervated diabetics and diabetics, respectively) and medullar GLUT1 protein in control rats, but reverted the cortical GLUT1 protein rise determined by diabetes. Although kidney denervation in diabetic rats induced a decrease in cortical GLUT1 abundance toward normal levels, these levels did not reach those of normal animals. However, renal denervation did not determine any changes in urinary albumin and urinary TGF-beta1 in both diabetic (127.3+/-12 microg/24 h and 111.8+/-24 ng mg(-1) creatinine, respectively) and control rats (45.9+/-3 microg/24 h and 13.4+/-4 ng mg(-1) creatinine, respectively). In conclusion, early-phase renal denervation in streptozotocin-diabetic rats produces a normalisation of previously elevated cortical GLUT1 protein content, but is not enough for reverting the increased urinary TGF-beta1 and albuminuria of diabetes.

Albuminuria↗
PubMed1998

Changes in myosin mRNA and protein expression in denervated rat soleus and tibialis anterior.

Denervation differs from other models of reduced neuromuscular activation due to the absence of a nerve-muscle connection and limited data exists regarding the effects of denervation on myosin heavy chain (MHC) expression. Thus, adult MHC expression (I, IIa, IIx, IIb) was studied in the rat soleus and tibialis anterior (TA) at the mRNA and protein levels 2, 4, 7, 10, 14, and 30 days following sciatic nerve transection. MHC protein content was quantified with SDS/PAGE and mRNA levels with the RNase-protection assay. Control soleus consisted predominately of type I MHC mRNA and protein, however, 4 days after denervation type I MHC mRNA was significantly decreased to 41+/-8% of control and continued to remain below control values. Soleus IIa mRNA was significantly elevated 7 and 10 days after denervation while IIx mRNA remained relatively constant until 30 days when it increased to 197+/-23% of control. At the protein level, soleus I MHC significantly decreased to 80% of the total while IIa MHC significantly increased to 20% of the total. At 30 days, Hx MHC protein accounted for 9.4+/-1.6% of the total soleus MHC protein. In the TA, IIb mRNA was significantly decreased to 57% of control by day 4 and remained significantly decreased for up to a month. TA IIx mRNA was also significantly decreased at 10 and 30 days after denervation. Similar to the soleus, TA Ha mRNA was significantly increased over control 7-14 days after denervation. There were no significant changes in TA MHC protein profile during one month of denervation. In both the soleus and TA, denervation significantly shifted the MHC mRNA profile as early as 4 days following denervation without any corresponding changes at the protein level. Significant mRNA changes without large changes in MHC protein composition continued throughout the denervation period suggesting that the muscle may be prevented from premature functional transitions by mechanisms such as decreased mRNA stability, translational block, or increased turnover of newly synthesized proteins.

Animals↗
PubMed1985

Chronic denervation of rat hemidiaphragm: maintenance of fiber heterogeneity with associated increasing uniformity of myosin isoforms.

During several months of denervation, rat mixed muscles lose slow myosin, though with variability among animals. Immunocytochemical studies showed that all the denervated fibers of the hemidiaphragm reacted with anti-fast myosin, while many reacted with anti-slow myosin as well. This has left open the question as to whether multiple forms of myosin co-exist within individual fibers or a unique, possibly embryonic, myosin is present, which shares epitopes with fast and slow myosins. Furthermore, one can ask if the reappearance of embryonic myosin in chronically denervated muscle is related both to its re-expression in the pre-existing fibers and to cell regeneration. To answer these questions we studied the myosin heavy chains from individual fibers of the denervated hemidiaphragm by SDS PAGE and morphologically searched for regenerative events in the long term denervated muscle. 3 mo after denervation the severely atrophic fibers of the hemidiaphragm showed either fast or a mixture of fast and slow myosin heavy chains. Structural analysis of proteins sequentially extracted from muscle cryostat sections showed that slow myosin was still present 16 mo after denervation, in spite of the loss of the selective distribution of fast and slow features. Therefore muscle fibers can express adult fast myosin not only when denervated during their differentiation but also after the slow program has been expressed for a long time. Light and electron microscopy showed that the long-term denervated muscle maintained a steady-state atrophy for the rat's life span. Some of the morphological features indicate that aneural regeneration events continuously occur and significantly contribute to the increasing uniformity of the myosin gene expression in long-term denervated diaphragm.

Animals↗
PubMed2003

Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats.

Inhibitors of differentiation (Id) proteins are repressors of myogenic regulatory factors and have been implicated in apoptosis and muscle atrophy during aging. Indeed, we have previously found that Id levels are elevated in muscles from old rodents, possibly as a consequence of loss of alpha-motoneurons during senescence. To determine if Id2 proteins increase after denervation and if this is accompanied by increased apoptosis in aged as compared with adult animals, the gastrocnemius and soleus muscles were denervated in 1 limb of Fischer 344 x Brown Norway rats aged 9 months (adult, n = 12) and 33 months (aged, n = 9), while the contralateral limb served as the intra-animal control. After 14 days, the muscles in each limb were removed. The levels of Id1, Id2, and Id3 mRNA and protein were significantly greater in muscles of old as compared with young adult rats. Denervation, however, did not significantly increase Id1, Id2, and Id3 mRNA in soleus or gastrocnemius muscles from either young or old rats. Also Id2 protein levels were similar in denervated and control muscles from young adult and old rats. In young adult rats only, denervation induced an increase in Id1 and Id3 protein levels in both the soleus (Id1 113%; Id3 900%) and gastrocnemius (Id1 86%; Id3 80%). Denervation induced a significant increase in caspase 8 in both soleus and gastrocnemius muscles from young (101% and 147%, respectively) and old rats (167% and 190%, respectively). Bax protein levels, as estimated by western blots, increased by 726% and 1087% after denervation in the soleus and by 368% and 49% in the gastrocnemius muscles of young and old rats, respectively. The data suggest that the denervation-induced muscle loss was at least partly due to apoptosis as indicated by elevated caspase 8 and Bax levels in denervated muscles. While Id2 may have a role in aging-induced sarcopenia, Id2 does not appear to directly regulate apoptosis during denervation. The elevated Id expression in muscles from aged animals is therefore not a direct consequence of loss of alpha-motoneurons during senescence.

Aging↗
PubMed1997

Evidence for decreased structurally determined preglomerular resistance in the young spontaneously hypertensive rat after 4 weeks of renal denervation.

OBJECTIVES: To study the effects of denervation of the kidney on renal vascular resistance at maximal dilatation and renal function during the development of hypertension in the spontaneously hypertensive rat (SHR). METHODS: SHR aged 6 weeks were subjected to left renal denervation or a sham-operation (n = 18 denervated, n = 13 sham). When they were aged 10 weeks, pairs of denervated and sham-operated left kidneys were perfused with 2% dextran in Tyrode's solution and pressure-flow and pressure-glomerular filtration rate (GFR) relationships at maximal vasodilation were established. The awake mean arterial blood pressure, in-vivo renal function and renal noradrenaline content were also measured. RESULTS: There were no significant differences between the pressure-flow relationships for denervated and sham-operated kidneys. However, there was a marked, parallel, shift leftwards in the pressure-GFR relationship (P < 0.001). Thus, the denervated kidneys commenced filtering at a lower threshold perfusion pressure than did the sham-operated ones. In-vivo renal plasma flow and GFR were significantly greater in the denervated left kidneys of SHR than they were in the contralateral kidneys. The noradrenaline content in denervated kidneys was 5 +/- 3% of that in innervated kidneys. The awake mean arterial pressure was 135 +/- 1 and 138 +/- 2 mmHg in the denervated and sham-operated groups respectively. CONCLUSION: Denervation of the kidney of SHR aged 6 weeks of age altered the pressure-GFR but not the pressure-flow relationship for these rats 4 weeks later. The results are compatible with there having been an increase in average preglomerular and a decrease in post-glomerular vessel lumen diameters. These changes suggest that the renal nerves affect the structural development of the renal vasculature in SHR.

Animals↗
PubMed1992

The effects of liver denervation on the regulation of hepatic biliary secretion.

Effects of liver denervation on bile formation were studied in eight dogs prepared with chronic biliary fistulas. The animals were studied in the basal state, after feeding, and during infusion of glucagon 50 ng/kg/min, secretin 2 U/kg/hr, or somatostatin 200 ng/kg/min. After this first set of experiments the animals underwent a total hepatic denervation that consisted of section of the hepatic ligaments and a careful dissection of the portal vein, hepatic artery, and common duct with stripping of all the surrounding connective tissue and topical application of phenol. The above experiments were then repeated. Denervation did not modify bile flow, or bile salts, cholesterol, or phospholipid concentration or output. Biliary response to glucagon and secretin was similar before and after denervation. Somatostatin had an anticholerectic effect in both intact and denervated animals, but significantly reduced bile salt output only in the intact dogs. Feeding had a choleretic effect pre- and postdenervation, and the infusion of somatostatin following feeding decreased bile flow to the same degree before and after denervation. In the intact animals the output of all three biliary lipids was reduced by somatostatin after feeding but they were unaffected by somatostatin after denervation. Moreover, cholesterol and phospholipid outputs were stable after feeding in intact animals, but significantly decreased after denervation. 14C-erythritol clearance studies indicated no change in the canalicular component of bile flow with denervation, except again during somatostatin suppression of feeding. These data indicate that basal bile flow is normal after denervation but that innervation may play an important role in the modulation of responses to somatostatin and more complex stimuli such as feeding.

Animals↗
PubMed2004

The outcome of renal denervation for managing loin pain haematuria syndrome.

OBJECTIVE: To evaluate the outcome of renal denervation for the treatment of loin pain-haematuria syndrome (LPHS), a rare syndrome of unknown cause associated with debilitating and intractable loin pain. PATIENTS AND METHODS: The case notes of 32 patients having 41 renal denervations were reviewed. Data collected included patient demographics, possible causes, cure or not after renal denervation, time to recurrence of pain after denervation and further operative intervention for managing LPHS. RESULTS: Full data were available for 24 patients (13 women; median age 43 years, range 28-74) having 33 denervations (eight bilateral and one repeat) with a median follow-up of 39.5 months. Most patients had no identifiable underlying cause although many had initially been diagnosed as having stone disease (42%) or pyelonephritis (25%), but with no corroborative evidence. All patients had been extensively investigated and had normal urine samples and cytology, and no abnormality on intravenous urography, renal tract ultrasonography and isotopic renography. Twenty-four renal denervations (73%) were followed by recurrent ipsilateral pain at a median (range) of 11 (0-120) months after surgery. Nine denervations (25%) in six men and two women were curative (median follow-up 16.5 months). Of those with recurrent pain, nine (38%) proceeded to nephrectomy, of whom three then developed loin pain on the contralateral side and two developed disabling wound pain. The analgesic requirement was less after eight non-curative denervations. There were no significant postoperative complications. CONCLUSIONS: Renal denervation has only a 25% success rate for managing pain associated with LPHS and should be used cautiously for this indication. Men had more benefit from the treatment; a third of patients had less requirement for analgesic after non-curative denervation.

Adult↗
PubMed1997

Increased sensitivity of gastrin cells to gastric distension following antral denervation in the rat.

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.

Animals↗
PubMed1975

Influence of activity on the passive electrical properties of denervated soleus muscle fibres in the rat.

The technique of direct electrical stimulation of denervated muscle was used to study the role of muscle activity per se in controlling the passive electrical properties of muscle fibres. 2. Specific membrane resistance and capacitance of the denervated and the denervated-stimulated muscle fibres were measured by a sinewave technique at frequencies between 5 and 240 Hz. The parameter values were constant at low frequencies up to a variable transition frequency and declined rapidly at higher frequencies. 3. Following denervation the low-frequency value of specific membrane resistance increased (2291 omega cm2 for 19-day denervated fibres vs. 766 omega cm2 for innervated fibres), the specific membrane capacitance declined (2-7 muF/cm2 vs. 3-6 muF/cm2) and the transition frequency shifted towards lower frequencies. The specific internal resistance was higher in denervated fibres (301 omega cm for 19-day denervated fibres vs. 240 omega cm in innervated fibres) apart from a transient decline after 5 days of denervation (164 omega cm). 4. Direct electrical stimulation for 2 weeks beginning on the 5th day after denervation restored all parameters listed above to their original values before denervation. 5. Stimulation arrested in most cases further atrophy from the time of stimulation but did not restore normal fibre size.

Animals↗
PubMed1977

Cation movements in normal and short-term denervated rat fast twitch muscle.

1. The earliest known change in rat fast muscle following denervation is a fall in resting membrane potential unaccompanied by change in membrane resistance. The present study tested the hypothesis that increased Na permeability (P(Na)) accounted for this early depolarization.2. In all experiments, rat extensor digitorum longus muscles were studied in vitro at 25 degrees C. Li uptake in vitro, used as a measure of P(Na), was greater in 1- and 2-day denervated muscles (and in 2-day denervated diaphragm) than in paired controls.3. The extra Li taken up by denervated muscle was not sequestered in an extracellular or freely exchangeable compartment, nor was it irreversibly bound.4. Measurements of resting membrane potential and of internal Na, K, and Li in Krebs solution before and 2 hr after replacement of NaCl by LiCl, were used to compute the ratios P(Na)/P(K) and P(Li)/P(K) for normal or denervated muscles. P(Na) and P(Li) were similar relative to P(K) within each class of muscle.5. Both P(Na)/P(K) and P(Li)/P(K) ratios were elevated more than twofold in denervated muscle, as were most estimates of relative P(Li) approximated by the flux equation.6. These data, and measurement of resting membrane potential of normal muscle in 1 mM external K-Krebs solution, support the view that an electrogenic Na-K pump does not substantially contribute to this potential of normal or denervated muscle, and that the early depolarization after denervation results from increased P(Na).7. The Na-K pump of denervated muscle was as sensitive to ouabain as normal muscle. An effect of ouabain on P(Na) may explain previously noted differential effects of ouabain on normal and denervated muscle.

Animals↗
PubMed1982

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice.

1. The properties of denervated and fully innervated but paralysed soleus and extensor digitorum longus (e.d.l.) muscles were compared in mice.2. Muscles were paralysed by single or repeated injections of botulinum toxin into the right lower leg. Contralateral muscles were denervated at the same time by sciatic nerve section. Muscles were excised 3-20 days later and direct and indirect isometric twitch and tetanic tensions measured in vitro. ACh sensitivity was assessed from isometric contractions to various concentrations of bath-applied ACh perchlorate.3. Denervated muscles as expected from the work of others developed sensitivity to ACh earlier and more rapidly than paralysed muscles. A transient peak of sensitivity was reached after 7 days of denervation in soleus and after 8 days in e.d.l. However 2 days later the sensitivity of muscles fully paralysed to nerve twitch and tetanic stimuli was not significantly different from that of denervated muscles.4. In both e.d.l. and soleus the direct tetanus/twitch ratios declined in paralysed and denervated muscles. The decline was initially more rapid in denervated than paralysed soleus, but the ratios for paralysed and denervated muscles were not significantly different after 10 days in either muscle. By this time there were no differences in the absolute strengths of the paralysed and denervated muscles.5. It is concluded that the ACh sensitivity and dynamic properties of fully paralysed mouse muscles become equal to those of denervated muscles once the acute effects associated with nerve degeneration are past. This result is consistent with the idea that normal neuronal control of extrajunctional mammalian skeletal muscle properties is mediated solely by means of activity.

Acetylcholine↗
PubMed1985

Excitation-contraction coupling and charge movement in denervated rat extensor digitorum longus and soleus muscles.

K contractures and asymmetrical charge movement were recorded in extensor digitorum longus (e.d.l.) and soleus muscles that had been denervated for 2-68 days. The relationship between maximum tension during a K contracture and membrane potential shifted to more negative potentials in denervated e.d.l. muscles (by -25 mV on average) and to a lesser extent in soleus (by -8 mV on average), and became steeper, more so in e.d.l. than soleus. Apart from an early negative shift of -11 mV in the voltage dependence of tension in e.d.l. muscles during the first week, the other changes in K contractures following denervation occurred progressively during the first 3 weeks and then stabilized. There was a clear difference in charge movement in denervated e.d.l. fibres but little change in denervated soleus fibres, so that the characteristics of charge movement in e.d.l. and soleus became very similar. The maximum amount of charge movement fell from an average normal value of 23 nC/microF to 6 nC/microF in e.d.l. within the first 2 weeks. The voltage sensitivity shifted to more negative potentials (by about -12 mV on average) within the first week. There was no significant change in the slope of the relationship between charge and membrane potential. The effects of denervation on charge movement could only partly explain the changes in K contractures. The only obvious parallels were the early negative shift in the voltage dependence of charge movement and tension in denervated e.d.l. fibres. The other changes in K contractures in denervated fibres could be due to a change in the relationship between charge movement and Ca concentration in the myoplasm or an increase in the Ca affinity of the myofilaments. Although charge movement fell to about a quarter of normal in denervated e.d.l. fibres, membrane capacity increased approximately 3-fold. A similar increase in capacity in soleus fibres was not associated with a change in charge movement. Fewer indentations were seen in denervated than in normal e.d.l. fibres. The decrease paralleled the fall in charge movement.

Action Potentials↗
PubMed1979

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.

Animals↗
PubMed1984

Evaluation of topical phenol as a means of producing autonomic denervation of the liver.

Topical application of 90% phenol around the bile duct, portal vein, and hepatic artery, as well as along each of the three hepatic ligaments was tested for effectiveness of rapid and chronic denervation in cats. Because phenol produces nonselective nerve degeneration, it was assumed that proof of functional sympathectomy was adequate proof of disruption of parasympathetic and afferent nerves as well. Functional sympathetic neurons were evaluated by measuring physiological responses to direct electrical stimulation of the anterior hepatic plexus. Acute or rapid denervation was assessed by the degree of rise in portal blood pressure produced by nerve stimulation. Complete denervation appeared within 20 min and was still present by 80 min postapplication. Chronic denervation was tested by applying the phenol and recovering the cats for 6-14 days. An equal number (n = 6) of sham-denervated cats were compared. Phenol denervation did not alter basal glucose, insulin or glucagon levels, hematocrit, blood pressure, or hepatic glycogen levels. These variables are a good index of stress and metabolic status. Nerve stimulation in the chronic sham group raised portal pressure, arterial pressure, and blood glucose levels, whereas the chronic-denervated group showed no responses. The health of the two groups appeared normal with the sole difference being that the painted tissues were mildly discolored and more adhesions appeared in the phenol-denervated set. Thus phenol is a useful tool for producing hepatic denervation. It is less traumatic, faster, and more certain than surgical denervation. In addition, the hepatic lymphatics can be preserved using the topical application of phenol.

Administration, Topical↗
PubMed2004

M-cadherin transcription in satellite cells from normal and denervated muscle.

Satellite cells (SC) in adult muscle are quiescent in the G0 phase of the cell cycle. In the present study we determined whether SC after denervation upregulate M-cadherin, an adhesion molecule that is upregulated with differentiation and fusion. We also monitored primary cultures of SC from denervated muscle for expression of the transcription factors of the MyoD family to determine whether SC from denervated muscle can be activated in vitro. Hindlimb muscles of rats were denervated under anesthesia, and rats were killed after 2-28 days. The SC of the denervated limbs were pooled and either assessed for M-cadherin mRNA by using real-time RT-PCR or cultured in vitro. The cultures were processed for RT-PCR or immunofluorescence for expression of the transcription factors of the MyoD family. Hindlimb muscles of M-cadherin knockout mice were denervated under anesthesia, mice were killed after 2-28 days, and cells were stained for beta-galactosidase activity by X-gal histochemistry. In vitro, primary SC cultures from rat muscle denervated for 2-28 days expressed transcripts of myf5, MyoD, myogenin, and MRF4 as SC from normal innervated muscle. In vivo, M-cadherin transcription was not upregulated in SC from denervated rat muscle when compared with normal muscle. Moreover, beta-galactosidase activity was not detected in denervated mouse muscle. The finding that SC do not upregulate M-cadherin after denervation supports the notion that they remain in the G(0) phase of the cell cycle in vivo. However, the cells retain the capacity to pass through the proliferative and differentiative program when robustly stimulated to do so in vitro.

Animals↗
PubMed1992

Recovery of arterial pressure control after partial baroreceptor denervation in awake rabbits.

We examined recovery of control of heart rate (HR) and total peripheral resistance (TPR) by arterial baroreceptors after bilateral carotid sinus and aortic denervation or unilateral carotid sinus and aortic denervation in conscious rabbits. In one group of animals, HR responses to changes in mean arterial pressure (MAP) after injection of nitroglycerin or phenylephrine were measured in control studies and at 2, 5, 10, and 15 days after partial baroreceptor denervation. All denervation procedures increased MAP and HR at 2 and 5 days after denervation. Reflex sensitivity decreased to 57-67% of control on day 2 after denervation. HR responses recovered by day 10 after bilateral aortic or carotid sinus denervation; however, recovery following unilateral denervation was less complete. In a second group of animals, studied after implantation of aortic flowmeters, TPR changes following reduction in cardiac output by inferior vena caval occlusion were 49% of control responses on day 2 after denervation and returned close to control level on day 5. Controls of HR and TPR recovered substantially and were not significantly different from control 10 days after partial denervation. Recovery apparently occurred through the remaining arterial baroreceptors, possibly due to central reorganization of reflex pathways.

Animals↗
PubMed2006

Decreased expression of aquaporin water channels in denervated rat kidney.

AIMS: A neural mechanism regulating aquaporin (AQP) water channels in the kidney was investigated. METHODS: Male Sprague-Dawley rats were used. Renal denervation was induced by painting the renal vessels with 10% phenol. The expression of AQP1-4 proteins was determined in the denervated and contralateral kidneys. The expression was also examined in rats which were renally denervated and subjected to water restriction or deoxycorticosterone acetate (DOCA)-salt treatment. RESULTS: Following the unilateral denervation, tissue contents of norepinephrine were significantly decreased in the denervated kidney, while increased in the contralateral kidney. Accordingly, the expression of AQP1-4 proteins was decreased by 15-40% in the denervated kidney, and increased by 30-50% in the contralateral kidney. Immunohistochemistry of AQP2 confirmed its decreases in the denervated kidney and increases in the contralateral kidney. In bilaterally denervated rats, the urine flow increased along with decreased osmolarity. The water restriction increased the expression of AQP channels, however, the magnitude of which was lower in the denervated than in the contralateral kidney. Renal denervation decreased the degree of DOCA-salt hypertension, along with lower expression of AQP channels. CONCLUSION: It is suggested that the sympathetic nerve should play a specific excitatory role in the regulation of AQP channels in the kidney.

Adenylyl Cyclases↗
PubMed1985

Mechanisms of supersensitivity to sympathomimetic amines in the chronically denervated heart of the conscious dog.

Mechanisms of denervation supersensitivity to sympathomimetic amines were studied in conscious animals. Norepinephrine, 0.1 micrograms/kg, increased left ventricular dP/dt significantly more (4208 +/- 828 mm Hg/sec) in dogs with cardiac denervation than in intact dogs (1029 +/- 280 mm Hg/sec), P less than 0.01, whereas responses to isoproterenol were similar in both groups. Denervation supersensitivity to isoproterenol could be demonstrated only after opposing reflex effects were blocked. After ganglionic blockade, norepinephrine still induced 2- to 3-fold greater increases in left ventricular dP/dt and 3- to 7-fold greater increases in heart rate in cardiac-denervated dogs, whereas isoproterenol and prenalterol, not taken up by presynaptic nerve endings, elicited only 40%-50% greater increases in left ventricular dP/dt and heart rate in dogs with cardiac denervation. The density of beta-adrenergic receptors [( 3H]dihydroalprenolol) was elevated (P less than 0.01) in denervated left ventricles (105 +/- 6.9 fmol/mg protein, n = 8) compared to normal left ventricles (70 +/- 6.3 fmol/mg protein, n = 12). This was accompanied by enhanced isoproterenol-mediated adenylate cyclase activity. However, muscarinic cholinergic receptor density, [( 3H]quinuclidinyl benzilate), decreased from control levels of 251 +/- 11 fmol/mg protein (n = 7) to 193 +/- 14 fmol/mg protein (n = 6). Thus, chronic cardiac denervation results in upregulation of the beta-adrenergic receptor and down-regulation of the muscarinic receptor. The increased beta-adrenergic receptor density and adenylate cyclase stimulation correlated well with the amount of denervation supersensitivity to isoproterenol and prenalterol, but accounted for only a minor fraction of denervation supersensitivity to norepinephrine. The major mechanism of denervation supersensitivity to norepinephrine appears to involve lack of the norepinephrine reuptake.

Adenylyl Cyclases↗