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PubMed1990

Actions of angiotensin peptides after partial denervation of the solitary tract nucleus.

We determined the excitatory effects of direct nucleus tractus solitarii injection of angiotensin peptides after the sinoaortic nerves were cut unilaterally in rats under halothane anesthesia. Twenty-four hours later, recordings of mean arterial pressure and heart rate were obtained during injections of 2.5 ng angiotensin II or angiotensin-(1-7) in chloralose-urethane-anesthetized rats. Both peptides caused reductions in pressure and heart rate after nucleus tractus solitarii injections. In unilateral sinoaortic denervated rats, the hypotension and bradycardia produced with angiotensin II injections in either the ipsilateral (denervated) or contralateral (nondenervated) nucleus tractus solitarii were comparable. Angiotensin-(1-7), however, produced a larger decrease in pressure on the denervated side when compared with the nondenervated side. There were no differences in baseline pressure or heart rate between control rats and those with unilateral sinoaortic denervations. The effects of both angiotensin II and angiotensin-(1-7) were blocked by previous administration of the angiotensin II antagonist [Sar1,Thr8]angiotensin II into the nucleus tractus solitarii. Assessment of angiotensin II binding sites in the solitary-vagal complex 24 hours after denervation showed a 13% reduction in angiotensin receptors. These findings confirm that both angiotensin II and angiotensin-(1-7) express biological activity through receptor-mediated actions in the dorsal medulla oblongata. That the effects produced by angiotensin II do not require the integrity of baroreceptor input further suggests that the receptors responsible for the acute cardiovascular actions of this peptide reside on postsynaptic elements in the vagal-solitary complex.

Angiotensin I↗
PubMed1995

Renal denervation attenuates the sodium retention and hypertension associated with obesity.

Recent studies have indicated that obesity is associated with hypertension, sodium retention, and increased sympathetic nervous system activity. The purpose of this study was to determine the role of renal nerves in mediating the sodium retention and hypertension associated with obesity. We determined the hemodynamic and renal excretory responses to a high-fat diet in control (n = 6) and bilaterally renal-denervated (n = 7) chronically instrumented dogs. After a control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In response to a high-fat diet, body weight increased from 19.9 +/- 2.2 to 29.9 +/- 2.4 kg in the control group and from 21.1 +/- 2.0 to 32.4 +/- 1.9 kg in the bilaterally renal-denervated group. Heart rate increased from 81 +/- 8 to 113 +/- 7 beats per minute in the control group and from 79 +/- 7 to 103 +/- 8 beats per minute in the bilaterally renal-denervated group. Arterial pressure increased significantly from 95 +/- 2 to 109 +/- 4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the bilaterally renal-denervated group did not significantly increase arterial pressure (which went from 87 +/- 3 to 90 +/- 4 mm Hg). Furthermore, the decrease in sodium excretion in response to the high-fat diet was significantly greater in the control group than in the bilaterally renal-denervated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats.

Sinoaortic and cardiac baroreflexes exert important control over renal sympathetic nerve activity. Alterations in these reflex mechanisms contribute to renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in normotensive Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In all rat strains, this yielded systems whose correlation dimensions converged to similar low values over the embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor denervation was associated with decreases in the correlation dimensions (Sprague-DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/-0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive rats had a similar correlation dimension, which was unaffected by complete baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for the greatest Lyapunov exponent, which decreased to a lesser extent after complete baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity is associated with a greater decrease in the chaotic behavior of renal sympathetic nerve activity in normotensive compared with hypertensive rats. This suggests that the central neural mechanisms that regulate renal sympathetic nerve activity in response to alterations in cardiovascular reflex inputs are different in spontaneously hypertensive rats from those in Sprague-Dawley and Wistar-Kyoto rats.

Anesthesia↗
PubMedDate not supplied

Renal denervation at weaning retards development of hypertension in New Zealand genetically hypertensive rats.

The development of hypertension was studied in 3 to 13-week old New Zealand genetically hypertensive (NZGH) rats subjected to bilateral renal denervation (D) or sham operations (S) at 4 weeks of age. Denervation retarded the development of hypertension and delayed the establishment of stable hypertension; blood pressure of D-NZGH rats was 15-40 mm Hg lower than that of S-NZGH rats from 3 to 7 weeks after surgery, but was similar in the two groups thereafter. D-rat renal catecholamine content was reduced to 17% of control at 1 week after surgery; by the fourth week post surgery, renal catecholamine content had risen to 40% of control, and blood pressure of the D-group had begun to rise, suggesting that spontaneous renal reinnervation prevented the antihypertensive effect of renal denervation from being a permanent one. During the period when blood pressure of the S-rats was greater than that of the D-rats, urinary sodium excretion of the two groups was not significantly different, suggesting that over this interval the relationship between blood pressure and urinary sodium excretion shifted to the right along the pressure axis in the S-rats but not in the renal denervated rats. Throughout the 60-day period of observation, urinary excretion of prostaglandin E2 and kallikrein did not differ between the renal-denervated and sham-operated rats.

Animals↗
PubMed1986

Selective vasodilation produced by renal denervation in adult spontaneously hypertensive rats.

The kidneys of adult male spontaneously hypertensive rats (SHR) were denervated, and systemic and regional blood flows were measured 3 to 5 hours or 5 days after denervation. Arterial pressure was reduced 20 to 27% in denervated SHR during both periods compared with that in sham-operated SHR (iliolumbar blood vessels painted with phenol). This hypotensive response was produced by a 32 to 35% reduction in total peripheral resistance. At 3 to 5 hours and at 5 days, a major decrease in total peripheral resistance was produced by vasodilation in the kidneys and splanchnic organs. Acute urine output, sodium excretion, and plasma renin activity in response to a saline load were not different between sham-operated and denervated SHR. The decreased total peripheral resistance in denervated SHR may have been secondary to a decreased central sympathetic nerve activity revealed by a decreased maximum response to ganglionic blockade. The results suggest that a pathophysiological link may exist between the kidneys and splanchnic organs in genetic hypertension and that specific efferent antiadrenergic or antiafferent nerve therapy, or both, in the kidney may lead to substantial specific decreases not only in renal vascular resistance but also in splanchnic vascular resistance and total peripheral resistance.

Animals↗
PubMed1973

The adrenergic control of lower esophageal sphincter function. An experimental model of denervation supersensitivity.

To evaluate the adrenergic regulation of lower esophageal sphincter (LES) function, LES pressure, LES relaxation during swallowing, and blood pressure were measured in the anesthetized opossum, Didelphis virginiana, during intravenous administration of alpha and beta adrenergic agonists and antagonists. Studies were done in controls and animals adrenergically denervated with 6-hydroxydopamine. Alpha adrenergic agonists (norepinephrine, phenylephrine) increased LES pressure and blood pressure, whereas a beta adrenergic agonist (isoproterenol) decreased both pressures. Alpha adrenergic antagonism (phentolamine) reduced basal LES pressure by 38.3+/-3.8% (mean +/-SEM) (P < 0.001). Beta adrenergic antagonism (propranolol) had no significant effect on either basal LES pressure or percent of LES relaxation with swallowing. After adrenergic denervation with 6-hydroxydopamine, basal LES pressure was reduced by 22.5+/-5.3% (P < 0.025) but LES relaxation during swallowing was unaltered. In denervated animals, both LES pressure and blood pressure dose response curves showed characteristics of denervation supersensitivity to alpha but not to beta adrenergic agonists. These studies suggest: (a) a significant portion of basal LES pressure is dependent upon alpha adrenergic stimulation; (b) LES relaxation during swallowing is not an adrenergically mediated response; (c) the LES pressure response to alpha adrenergic agonists after 6-hydroxydopamine may serve as a model of denervation supersensitivity in the gastrointestinal tract.

Animals↗
PubMed1997

Changes in myosin expression in denervated laryngeal muscle.

The effects of chronic denervation on the myosin heavy chain (MyHC) content and muscle fiber type composition of rat laryngeal muscles are described. The posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were removed 3 weeks, 3 months, and 6 months after recurrent laryngeal nerve sectioning. Myofibrillar adenosine triphosphatase staining of cryostat sections was performed, and fiber type percentages were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to separate MyHC isoforms, and densitometry was subsequently used for quantitative analysis. Unoperated animals served as controls. In the PCA muscle, denervation resulted in a progressive reduction in type I MyHC (the slow-contracting isoform) to an almost complete loss at 6 months, with a concomitant increase in type II MyHCs (fast-contracting isoforms, excluding type IIL). Type IIL MyHC (laryngeal-specific isoform) remained relatively constant up to 6 months after denervation. The myosin expression in the TA muscle, which contained only type II MyHCs, remained relatively constant with denervation. Changes in fiber type composition of the muscles described from tissue staining correlated with MyHC content. These findings in laryngeal muscle confirm the dependence of type I MyHC expression upon neural input, as has been found previously in limb skeletal muscles. Since the expression of all MyHCs except the IIL was modified after denervation in the PCA muscle, it is possible that the IIL isoform is maintained by factors that differ from those in the other skeletal myosins.

Animals↗
PubMed2004

Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium.

Inferior alveolar nerve denervation causes appreciable decreases in the distribution of epithelial rests of Malassez. To explore roles of the Malassez epithelium, we attempted to evaluate possible changes in dento-alveolar tissues surrounding this epithelium by experimental denervation. We found that denervation led to dento-alveolar ankylosis with a decrease in the width of the periodontal spaces. Interestingly, with regeneration of the Malassez epithelium 10 weeks after the denervation, the periodontal space width showed a correspondingly significant increase. These findings suggest that the Malassez epithelium may be involved in the maintenance of periodontal space and that sensory innervation might be indirectly associated with it. In addition, it is of interest that denervation activated root resorption of the coronal root surface and that the consequently resorbed lacunae were repaired by cellular cementum. It is suggested that Malassez epithelium may negatively regulate root resorption and induce acellular cementum formation.

Acid Phosphatase↗
PubMed1978

Effect of denervation on coxsackie A virus myositis in mice: an electronmicroscopic study.

Myositis induced by Coxsackie A4 and A9 viruses was investigated in the gastrocnemius muscles of suckling mice and adult mice with denervation. Denervation markedly increased the susceptibility of adult mice to Coxsackie A virus infection, and this effect was initiated as early as 1 day after denervation. Light microscopy demonstrated inflammation and necrosis in the denervated gastrocnemius muscle of adult mice, whereas muscle from the contralateral leg showed only infrequent, mild, focal myositis. Ultrastructually, crystalline arrays of virus particles were seen in the infected muscle fibers and in the phagocytes of both suckling and adult mice. Nuclear alterations, especially in the myotubes, and a characteristic compound membrane-vesicle complex (CMVC) in the sarcoplasm, developed simultaneously. Replicating and fusing myoblasts, activated as part of the regenerative process after denervation, appeared to be closely associated with the susceptibility of muscle to Coxsackie A virus infection.

Animals↗
PubMed1983

The failure of oxygen breathing to decrease the myocardial contractile force in denervated dogs.

This study was done to discover whether or not the oxygen-induced depression of sympathoadrenal activity contributes to a reduction of myocardial contractile force during oxygen breathing. In 10 open-chest dogs, myocardial contractile force was measured using a myocardial strain gauge arch during air and oxygen breathing before denervation (intact heart) and after bilateral vagotomies, sympathectomies and adrenalectomies with the intravenous administration of propranolol, phenoxybenzamine and atropin (denervated heart). One hundred percent oxygen breathing caused similar increases in arterial pO2 in both the intact (from 94 +/- 10 to 442 +/- 25 mmHg) and the denervated dogs (from 113 +/- 11 to 456 +/- 15 mmHg). Coronary blood flow measured at the left anterior descending coronary artery was reduced by oxygen breathing from 28.4 +/- 3.4 to 21.7 +/- 2.3 ml/min in the intact dogs, and from 19.4 +/- 3.4 to 14.9 +/- 2.6 ml/min in the denervated dogs. Myocardial contractile force was significantly reduced by oxygen breathing in the intact dogs (a reduction of 5.8 +/- 1.4%). In the denervated dogs, on the other hand, no significant changes in myocardial contractile force was seen. This study suggests that the reduction in myocardial contractile force is mediated through sympathoadrenal activity, and thus, is abolished by sympathoadrenal blockade.

Adrenalectomy↗
PubMed1981

Influence of sino-aortic baroreceptor denervation on catecholamines, catecholamine-synthesizing enzymes and choline acetyltransferase activity in the brainstem nuclei of the rat.

At one week after sino-aortic baroreceptor denervation in the rat, aortic blood pressure and plasma contents of epinephrine and dopamine beta-hydroxylase (DBH) activity were elevated during resting and conscious states. Stress-induced elevation of blood pressure and plasma epinephrine were markedly pronounced. These changes disappeared at four weeks after denervation. Sino-aortic deafferentation decreased choline acetyltransferase (ChAc) activity in the nucleus tractus solitarii (NTS) and locus coeruleus (LC) and increased DBH activity, norepinephrine levels, phenylethanolamine N-methyltransferase (PNMT) activity and epinephrine levels in the LC, accompanied with a reduction of DBH activity and norepinephrine contents in the nucleus hypothalamicus posterior. These alterations were confirmed one week after denervation but did not persist for a period of four weeks. At four weeks after denervation, ChAc activity was significantly decreased in the nucleus dorsalis nerve of the vagi but not in ;the nucleus ambiguus. During the transient hypertensive phase, sino-aortic deafferentation did not alter DBH and PNMT activities in the NTS, A2 cell and A1 cell areas, and both catecholamine levels in the NTS. In conclusion, sino-aortic denervation transiently decreased ChAc activity in the NTS and LC, and enhanced synthesis and accumulation of norepinephrine and epinephrine in the LC accompanied with a decrease in norepinephrine contents and DBH activity in the nucleus hypothalamicus posterior, causally resulting in short-lasting labile hypertension and activation of the adrenal medulla.

Animals↗
PubMed1994

Effects of unilateral phrenic nerve denervation on diaphragm contractility in rat.

We examined the early effects of phrenic nerve denervation on the diaphragm muscle 1, 3, 7 and 14 days after unilateral denervation in rats. In the denervated hemidiaphragms, force frequency curves at 3, 7 and 14 days decreased significantly by 51%, 50% and 38% respectively of the peak tension of the force frequency curves of the diaphragms of rats with sham operation. Twitch tensions increased significantly at 14 days, and contraction times and half relaxation times slowed significantly at 3, 7 and 14 days. The tensions of denervated diaphragms at 5 min during the fatigue runs was significantly increased at 14 days. As determined by histological staining, the mean cross sectional area of fast-twitch fibers (type II) decreased significantly from 2,742 (sham) to 1,599 microns (14 days), but that of the slow-twitch fibers (type I) did not change significantly during the same period. These findings suggest that, during the first two weeks of denervation, fast twitch fibers (type II) atrophy more rapidly than slow twitch fatigue resistant fibers (type I), as confirmed by the contractile properties and histological findings.

Adenosine Triphosphatases↗
PubMed2000

Effects of short-term denervation and subsequent reinnervation on motor endplates and the soleus muscle in the rat.

The rat sciatic nerve was locally frozen, and changes in the nerve, motor endplates, and the soleus muscle were examined for up to 6 weeks by light and electron microscopy. The wet weights of denervated soleus muscles compared with contralateral values progressively declined to a minimum at 2 weeks after injury (60.7 +/- 2.5%) and began to reverse following 3 weeks. The sciatic nerve thoroughly degenerated after freezing. However, numerous regenerated myelinated and thin nerve fibers were observed at 3 weeks. They were considerably enlarged but still smaller than normal counterparts at 6 weeks postoperatively. Nerve terminals containing synaptic vesicles of endplates disappeared at day 1 and mostly reappeared at 3 weeks (about 70% of the endplates). All endplates examined were reinnervated at 4, 5, and 6 weeks. On the other hand, postsynaptic folds of muscle fibers seemed to be only slightly influenced by denervation or reinnervation. Ultrastructural alterations of myofibrils, in particular the loss of register, immediately appeared after denervation, spread progressively, peaked at 2 weeks, ameliorated following reinnervation, and became significantly normalized at 6 weeks after freezing. The proportion of type II fibers in the soleus muscle similary showed an increase and a decrease with a short delay in response to denervation and reinnervation, respectively. This study clearly demonstrated that the nerve supply affects the ultrastructural integrity of skeletal muscles. In addition, changes in the endplates and the soleus muscle evaluated in this study after short-term denervation are largely reversible following reinnervation.

Animals↗
PubMed1999

Effect of renal denervation on the compensatory renal growth following nephrectomy in the cat.

The purpose of this study was to clarify the effect of denervation on the mass of the remaining kidney with or without unilateral nephrectomy using adult cats. The animals were divided into 4 groups: (1) control group, the weights of the right and left kidneys were measured intact in 5 cats; (2) nephrectomy group (Nx, n = 5 cats), the right kidney was removed and the left kidney was weighed 3-5 d after nephrectomy; (3) nephrectomy and denervation group (Nx+Dx, n = 7 cats), the left kidney was weighed on the 7th day after surgery in which the left kidney was denervated and the right kidney was removed; and (4) denervation group (Dx+Dx, n = 5 cats), both kidneys were weighed on the 7th day after denervation of the kidneys. In the control group, the left and right kidney weights per body weight (LKW and RKW) were the same (LKW, 0.74 +/- 0.06%; RKW, 0. 74 +/- 0.07%). In the Nx group, LKW increased to 0.90 +/- 0.03% 3-5 d after nephrectomy, although RKW of the removed kidney was 0.66 +/- 0.01%. In the Nx+Dx group, LKW increased to 0.97 +/- 0.15%, which was similar to that of the Nx group. In the Dx+Dx group, LKW (0.56 +/- 0.05%) and RKW (0.54 +/- 0.05%) were significantly less than those in the control group. We conclude that the renal nerves may contribute to maintaining the renal mass and that the neural effect on compensatory growth following nephrectomy may be covered by other growth factors.

Adaptation, Physiological↗
PubMed1977

Acid secretory responses to histamine, pentagastrin, and feeding before and after vagal denervation of fundic pouches in cats.

Dose-response curves for acid output to histamine, pentagastrin and feeding were determined in cat before and after vagal denervation of the fundic pouch. Before denervation, the maximal response to the three stimulants was equal. Denervation reduced the acid response to histamine by decreasing the secretory capacity, and to pentagastrin by decreasing both the secretory capacity and sensitivity of the oxyntic glands. In this respect the effect of local and truncal vagotomy is equal in cats. The reduction of the response to feeding was greater than to histamine and pentagastrin. In the denervated pouch, the maximal response to feeding amounted to two-thirds of that to histamine and pentagastrin. This demonstrates that feeding does not release enough gastrin to induce maximal rate of acid secretion in the absence of vagal impulses. Nevertheless, feeding and pentagastrin produced equal maximal responses before denervation. This suggests that vagal impulses during feeding produce greater enhancement than basal vagal tone of the acid response to submaximal doses of gastrin.

Animals↗
PubMed1985

Significant bleeding at kidney resection after experimental denervation.

The effects of microsurgical denervation of the kidney on blood loss, bleeding time, platelet count and APT time in standardized kidney resection were studied in rats. The renal nerves running alongside the blood vessels were stained, identified and resected with a microsurgical technique. One week after the denervation, the blood loss and bleeding time at kidney resection were significantly greater than in control rats (without denervation). The bleeding resulted in reduced haemoglobin and haematocrit values, but the platelet count and APT time were unchanged. Platelet aggregation was not influenced by the denervation procedure. The increased bleeding at parenchymal kidney resection in the denervated rats was regarded as a consequence of interrupted nerve supply to the kidney. The effects on bleeding may have implications for renal surgery in humans.

Animals↗
PubMed1978

Effects of alpha-bungarotoxin and reversible cholinergic ligands on normal and denervated mammalian skeletal muscle.

alpha-Bungarotoxin (BuTX; 5 micrograms/ml) completely blocked the endplate potential and extrajunctional acetylcholine (ACh) sensitivity of surface fibers in normal and chronically denervated mammalian muscles, respectively, in about 35 min. A 0.72 +/- 0.033 mV amplitude endplate potential returned in normal muscle fibers after 6.5 hr. of washout of alpha-BuTX, and an ACh sensitivity of 41.02 +/- 3.95 mV/nC was recorded in denervated muscle after 6.5 hr of wash (control being 1215 +/- 197 mV/nC). A two-step reaction of BuTX with binding sites which may allosterically interact is postulated. Several pharmacologic differences were noted between the ACh receptors at the normal endplate and those appearing extrajunctionally following denervation. In normal innervated muscles exposed to BuTX in the presence of 20 microM carbamylcholine or decamethonium, washout of both drugs restored twitch to control levels within 2 hr. Endplate potentials large enough to initiate action potentials were also recorded in most surface fibers. In contrast, these agents, in much higher concentrations (50 microM), were almost ineffective in preventing BuTX blockade of ACh sensitivity in denervated muscle. Hexamethonium (10 and 50 mM) depressed neuromuscular transmission and blocked the action of BuTX in normal muscle in a dose-dependent fashion. On the extrajunctional receptors, hexamethonium (50 mM) was ineffective in protecting against BuTX. We may conclude that at the normal endplate region there are two distinct populations of ACh receptors, both of which react with cholinergic ligands and BuTX, but that a small population (representing congruent to 1% of the total) reacts with BuTX reversibly. Our findings further suggest a clear distinction between ACh receptors located at the normal endplate region and those of the extrajunctional region of the chronically denervated mammalian muscle.

Acetylcholine↗
PubMed1982

Decrease in sympathetic nervous system activity and attenuation in response to stress following renal denervation in the one-kidney one-clip Goldblatt hypertensive rat.

We have found that renal denervation in the one-kidney one-clip Goldblatt hypertensive rat results in an attenuation of the hypertension associated with a decrease in sympathetic nervous system activity. To test further the hypothesis that the renal nerves (afferents) contribute to the maintenance of hypertension in this model by modulating sympathetic nervous system activity, plasma norepinephrine and epinephrine changes in response to stress were compared in hypertensive sham-operated (n = 6), renal denervated (n = 6) and control (n = 7) animals. Stress was produced in conscious resting unrestrained animals by administering two brief electrical stimulations to the hindlimb. Resting plasma norepinephrine was significantly higher (P less than 0.01) in hypertensive sham-operated (420 +/- 41 pg/ml) compared to renal denervated (289 +/- 23 pg/ml) or control (296 +/- 25 pg/ml) animals. There was no difference in resting plasma epinephrine among the groups. In response to stress there were significantly greater absolute increases in plasma norepinephrine and epinephrine in hypertensive sham-operated animals compared to renal denervated and control groups, suggesting that the one-kidney one-clip rat exhibits an enhanced sympathoadrenal response to stress. The response to stress in renal denervated rats was the same as that in the control group. Taken together, these data support the concept that the renal afferent nerves modulate sympathetic nervous system activity in the one-kidney one-clip hypertensive rat.

Animals↗