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PubMed2006

Denervation does not change the ratio of collagen I and collagen III mRNA in the extracellular matrix of muscle.

Denervation or inactivity is known to decrease the mass and alter the phenotype of muscle and the mechanics of tendon. It has been proposed that a shift in the collagen of the extracellular matrix (ECM) of the muscle, increasing type III and decreasing type I collagen, may be partially responsible for the observed changes. We directly investigated this hypothesis using quantitative real-time PCR on muscles and tendons that had been denervated for 5 wk. Five weeks of denervation resulted in a 2.91-fold increase in collagen concentration but no change in the content of collagen in the muscle, whereas in the tendon there was no change in either the concentration or content of collagen. The expression of collagen I, collagen III, and lysyl oxidase mRNA in the ECM of muscle decreased (76 +/- 1.6%, 73 +/- 2.3%, and 83 +/- 3.2%, respectively) after 5 wk of denervation. Staining with picrosirius red confirmed the earlier observation of a change in staining color from red to green. Taken with the observed equivalent decreases in collagen I and III mRNA, this suggests that there was a change in orientation of the ECM of muscle becoming more aligned with the axis of the muscle fibers and no change in collagen type. The change in collagen orientation may serve to protect the smaller muscle fibers from damage by increasing the stiffness of the ECM and may partly explain why the region of the tendon closest to the muscle becomes stiffer after inactivity.

Animals↗
PubMed1986

Dietary obesity: brown fat denervation fails to alter development or recovery.

We assessed the effect of scapular brown adipose tissue (BAT) denervation on dietary obesity in adult female Sprague-Dawley rats. In rats maintained for 32 days on an obesity-inducing regimen, BAT denervation produced significant reductions in food intake (83.4 vs. 94.4 kcal/day), weight gain (66.0 vs. 103.5 g), and carcass fat (19.3 vs. 27.6%). A subgroup of denervates consuming as many calories as controls (94.1 kcal/day) failed to gain more weight (92.2 g) or accumulate more fat (25.4%) than controls. In rats developing obesity for 32 days followed by 8 days on laboratory chow, weight change was unaffected by denervation during either weight gain (89.4 vs. 87.1 g for controls) or weight loss (21.2 vs. 22.1 g) phases, as was carcass fat (21.0 vs. 20.4%). BAT norepinephrine utilization was unchanged in nondenervated obese rats and those recovering from obesity. We did not, therefore, find evidence that under these experimental conditions sympathetic activation of BAT countered obesity during overconsumption or contributed to recovery from obesity.

Adipose Tissue↗
PubMed1987

Sinoaortic denervation in the nonhuman primate.

There is considerable controversy as to whether removal of baroreceptor input by sinoaortic deafferentation leads to a sustained hypertension in quadripeds. Because of the importance of the baroreflex during postural changes, the effects of baroreceptor denervation may be even more profound in the primate. In this study, six adult male baboons (Papio anubis) were maintained on a tether system to examine the acute and sustained effects of aortic and combined carotid sinus and aortic baroreceptor deafferentation. Mean arterial pressure (MAP) averaged over 24 h increased from 86 +/- 4.0 to 105 +/- 5.5 mmHg after aortic denervation. One week after sinoaortic deafferentation, arterial pressure rose to 129 +/- 12.9 mmHg and then receded to 97 +/- 4.4 mmHg at 4 wk postdenervation. The lability of arterial pressure (measured as the mean of the standard deviations over 24 h) did not change with aortic denervation but increased at 1 and 4 wk after complete baroreceptor denervation. These studies indicate that baroreceptor deafferentation in the primate results in an acute increase in arterial pressure, the lability of arterial pressure, and heart rate. However, by 4 wk postdenervation, the level and lability of arterial pressure are decreased but remain significantly elevated.

Animals↗
PubMed1989

Atrial natriuretic peptide response to rapid atrial pacing in cardiac-denervated dogs.

The effects of rapid atrial pacing on central hemodynamics, plasma hormones, and renal function were investigated in eight control and nine cardiac-denervated dogs under chloralose anesthesia. Pacing at approximately 250 ppm for 60 min caused similar increases in pulmonary wedge and right atrial pressures, systemic vascular resistance, and plasma atrial natriuretic peptide (ANP) in both groups. In control dogs, pacing produced a fall in both plasma vasopressin (AVP) and plasma renin activity (PRA) and a rise in urine flow rate associated with an increase in free water but not sodium clearance. In contrast, in cardiac-denervated dogs, both plasma AVP and PRA increased during pacing; urine flow rate did not change, and marked sodium retention occurred. This study supports the concept that the increase in urine flow during rapid atrial pacing is mediated by inhibition of renin and AVP secretion through intact cardiac nerves. The secretion of ANP is unaffected by cardiac denervation. The natriuretic and vasodilator actions of high plasma ANP concentrations during rapid atrial pacing can be inhibited either by neurally mediated cardiorenal effects in normal animals or by stimulation of the renin-angiotensin system after cardiac denervation.

Animals↗
PubMed1990

Cardiovascular and neuroendocrine responses to baroreceptor denervation in baboons.

The purpose of this study was to describe the hormonal and blood pressure responses to partial (carotid sinus) and complete (carotid sinus + aortic arch) baroreceptor denervation in baboons. Experiments were performed in eight adult male baboons maintained on a tether system for the continuous measurement of mean arterial blood pressure (MAP) and heart rate (HR). Bilateral carotid sinus denervation (CSD) immediately increased MAP from 83 +/- 2.2 to 124 +/- 7.3 mmHg. MAP gradually decreased over the next 14 days to intact levels. There were also transient decreases in HR variability and increases in blood pressure variability after CSD. Subsequent denervation of the aortic arch to produce sinoaortic denervation (SAD) resulted in another abrupt large increase in MAP followed by a small but significant increase in MAP of 11 mmHg that was maintained for up to 4 wk after SAD. The short-term variability of HR and blood pressure was chronically decreased and increased, respectively, after SAD. Plasma renin activity, vasopressin, and epinephrine were not changed from intact levels either after CSD or SAD. Plasma norepinephrine was only transiently increased by CSD and chronically elevated by 72% over intact levels after SAD. Thus CSD in the baboon does not produce a sustained increase in MAP. SAD chronically increases MAP and is associated with evidence for an increased sympathetic tone. There is no indication that either increased renin secretion or vasopressin secretion contributes to the chronic cardiovascular effects of SAD in baboons.

Animals↗
PubMed1991

Sympathoadrenal activation in sinoaortic-denervated rats following endotoxin.

We evaluated the role of the baroreceptor reflex in mediating the sympathoadrenal activation during endotoxicosis, using acutely as well as chronically denervated rats. Three groups of experiments were conducted. In the first experiment, hemodynamic and plasma catecholamine responses following endotoxin (5 mg/kg iv) were measured in alpha-chloralose-anesthetized rats with acute sinoaortic baroreceptor denervation (SAD) or sham operation. In the second experiment, chronically sinoaortic-denervated rats and sham controls were used and experiments were conducted as in acute preparations. In the third experiment hydralazine (1 mg/kg iv) was given to chronically denervated rats and sham controls to evaluate the singular contribution of hypotension-evoked baroreflex disinhibition in the absence of endotoxin. In both acute and chronic preparations, endotoxin induced marked elevation of plasma norepinephrine and epinephrine in the presence as well as the absence of arterial baroreceptors (P greater than 0.05). Plasma catecholamines were significantly increased by hydralazine-induced hypotension in the sham group, but this elevation was far less than that induced by endotoxin. Hypotension alone did not significantly increase plasma catecholamines in SAD rats. These results suggest that the baroreflex is not the major factor in mediating sympathoadrenal activation during endotoxicosis and that non-baroreflex mechanisms may be involved in stimulating such activation.

Adrenal Glands↗
PubMed1992

Carotid chemoreceptors influence arterial pressure in intact and aortic-denervated rats.

The objective of the present study was to analyze the role of the arterial chemoreceptors in arterial pressure alterations produced by sinoaortic denervation (SAD) in rats. The mean arterial pressure during 2 h of continuous computerized beat-to-beat recordings was higher after aortic denervation (AD; 130 +/- 2 and 124 +/- 3 mmHg, respectively), lower after sinus denervation (SD; 101 +/- 1 and 101 +/- 3 mmHg), and remained unaltered after SAD (121 +/- 3 and 108 +/- 2 mmHg) 1 and 20 days after denervation compared with control rats (114 +/- 1 mmHg). Hypotensive effect of SD was confirmed when arterial pressure was recorded in the same animal before and after SD (from 112 +/- 2 to 103 +/- 2 mmHg). A similar effect was observed after isolated carotid body artery (CBA) ligation (from 114 +/- 3 to 104 +/- 3 mmHg). Furthermore, CBA ligation attenuated by 13% the hypertension after AD (from 136 +/- 2 to 118 +/- 3 mmHg). Bradycardic response to phenylephrine and arterial pressure variability were markedly altered by SAD and AD but remained normal after SD. In contrast, the chemoreflex (intravenous KCN) was abolished after SAD, SD, and CBA ligation but was preserved after AD. These data suggest that the arterial pressure alteration produced by SAD in rats represents the net effect of the abolition of inhibitory (baroreceptor deafferentation) and excitatory (chemoreceptor deafferentation) influences on the arterial pressure.

Animals↗
PubMed1995

Effect of liver denervation on glucose production during running in guinea pigs.

Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in contrast to the rich innervation in humans. The effect of liver denervation on glucose production during exercise was therefore studied in the guinea pig, a species with a rich sympathetic hepatic innervation comparable to that of humans. Guinea pigs were selectively liver denervated (n = 9) or sham operated (n = 8) and instrumented with a carotid and a jugular catheter. One week later they ran on a treadmill at 32 m/min for 20 min. Glucose turnover was evaluated by a primed constant-rate intravenous infusion of [3-3H]glucose. Arterial blood was sampled for analysis of hormones and metabolites. At rest, liver-denervated guinea pigs had lower glucose turnover and plasma concentrations of glucose, glycerol, and cortisol than control animals. During running, the increase in hepatic glucose production was similar in the two groups (4.1 +/- 0.8 vs. 3.8 +/- 0.7 mumol.min-1.100 g-1 in control animals) and so were hepatic (247 +/- 25 vs. 246 +/- 45 mmol glucose units/kg wet wt in control animals) and muscle glycogen concentrations at the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Reduced lactate transport in denervated rat skeletal muscle.

The purpose of this study was to investigate the effect of the neural regulation of contractile activity on lactate transport in skeletal muscle. Contractile activity of the rat soleus muscle was abolished by denervating the hindlimb muscles in one leg (3 days) while the sham-operated contralateral hindlimb muscles served as a control. Three days after surgery, lactate transport into the soleus muscle was measured in vitro, using incubated soleus muscle strips. Lactate uptake by the denervated soleus muscle was reduced compared with control (P < 0.05). The diffusive component of lactate transport was unaltered by denervation (P > 0.05). These results translated into a reduction in lactate carrier-mediated transport capacity (-68%) in the denervated soleus (P < 0.05). These studies indicate that loss of contractile activity results in a decrement of lactate transport, which is probably due to a reduction in the number of lactate carriers in the sarcolemma. Our results suggest that the inherent activity of the muscle is important in maintaining the lactate transport system.

Animals↗
PubMed1998

White adipose tissue sympathetic nervous system denervation increases fat pad mass and fat cell number.

The sympathetic nervous system (SNS) drive on white adipose tissue (WAT) was varied to test its effects on fat cell number (FCN) under conditions in which lipolysis would be minimized and therefore partially separable from SNS trophic effects. The inguinal subcutaneous WAT (IWAT) pad of Siberian hamsters was chosen because 1) it is innervated by the SNS, 2) short day (SD) exposure increases its SNS drive (approximately 250%) without proportionately increasing lipolysis, and 3) surgical denervation eliminates its SNS innervation. IWAT was either unilaterally surgically or sham denervated, while the contralateral pad was left intact. In long day- or SD-exposed hamsters (11 wk), IWAT denervation decreased norepinephrine content (approximately 80%) and increased fat pad mass (approximately 200%) and FCN (approximately 250 and approximately 180%, respectively) compared with the contralateral intact pads, but did not affect fat cell size (FCS). The denervation-induced increased FCN in SDs occurred despite naturally occurring decreased food intake. SDs decreased IWAT FCS regardless of the surgical treatment. These results support an important role of WAT SNS innervation in the control of FCN in vivo.

Adipose Tissue↗
PubMed1998

M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder.

In vitro bladder contractions in response to cumulative carbachol doses were measured in the presence of selective muscarinic antagonists from rats that had their major pelvic ganglion bilaterally removed. Denervation induced both hypertrophy and a supersensitivity of the bladders to agonist. The affinities in control bladders for antagonism of carbachol-induced contractions were consistent with M3-mediated contractions. Affinities in denervated bladders for 4-diphenlacetoxy-N-methylpiperidine methiodide (8.5) and p-fluoro hexahydrosilodifenidol (6.6) were consistent with M2-mediated contractions, although the methoctramine affinity (6.5) was consistent with M3-mediated contractions. Subtype-selective immunoprecipitation of muscarinic receptors revealed a 50% increase in total and a 60% increase in M2 receptor density with no change in M3 receptor density in denervated bladders compared with normal or sham-operated controls. This increase in M2 receptor density is consistent with the change in affinity of the antagonists for inhibition of carbachol-induced contractions and may indicate that M2 receptors or a combination of M2 and M3 receptors directly mediates smooth muscle contraction in the denervated bladder.

Animals↗
PubMed2001

Renal mRNA response to reduced perfusion pressure conserved despite denervation in mature ovine fetuses.

We hypothesized that renal denervation in mature ovine fetuses reduces renin mRNA response to 24 h of reduced renal perfusion pressure (RPP). Seven occluder (O) (132.4 +/- 1.2 days gestation) and six control (C) (131.5 +/- 1.2 days gestation) fetuses underwent left renal denervation. Postoperatively, O fetuses experienced 24 h of reduced RPP by suprarenal aortic occlusion. Femoral arterial blood pressure (FAB) and plasma active renin (pARC) and prorenin (pPRC) concentrations were obtained hourly for 6 h and at h 23 and 24. Renin mRNA was measured by RNase protection assay. We quantitated renin containing glomeruli by immunocytochemistry. Variables were compared by ANOVA. Mean O group FAB reduction from baseline was -6.60 +/- 0.41 mmHg. pARC and pPRC increased with occlusion, renal ARC and renal PRC did not increase with occlusion. No effect in renin mRNA or number of positive glomeruli was noted with denervation in the basal state; however, significant increases were noted in response to RPP irrespective of innervation status. In conclusion, 24 h or reduced RPP in mature ovine fetus increases renal renin mRNA and the immunocytochemical expression of renin. This response is conserved despite denervation.

Animals↗
PubMed2004

Effect of renal denervation on dynamic autoregulation of renal blood flow.

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Action Potentials↗
PubMed2002

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice.

Acute renal failure (ARF) contributes substantially to the high morbidity and mortality observed during endotoxemia. We hypothesized that selective blockade of the renal nerves would be protective against ARF during the early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip in mice]. At 16 h after LPS, there was no change in mean arterial pressure, but plasma epinephrine (4,604 +/- 719 vs. 490 +/- 152 pg/ml, P < 0.001), norepinephrine (2,176 +/- 306 vs. 1,224 +/- 218 pg/ml, P < 0.05), and plasma renin activity (40 +/- 5 vs. 27 +/- 2 ng x ml(-1) x h(-1), P < 0.05) were higher in the LPS-treated vs. control mice. The high plasma renin activity level decreased to the control level with renal denervation in endotoxemic mice. After intravenous injection of phentolamine (200 microg/kg), the decrement in mean arterial pressure was significantly greater in LPS-treated vs. control mice (19.4 +/- 3.5 vs. 8.1 +/- 1.5 mmHg, P < 0.01). Sixteen hours after LPS administration, there were significant decreases in glomerular filtration rate (52 +/- 18 vs. 212 +/- 23 microl/min, P < 0.01) and renal blood flow (0.58 +/- 0.08 vs. 0.85 +/- 0.06 ml/min, P < 0.01) in sham-operated mice. The decrement in glomerular filtration rate during endotoxemia was significantly attenuated in mice with denervated kidneys (32 vs. 79%). Moreover, there was no change in renal blood flow during endotoxemia in mice with renal denervation. The present results therefore demonstrate a protective role of renal denervation during normotensive endotoxemia-related ARF in mice, an effect that may be, at least in part, due to a diminished activation of the renin-angiotensin system.

Acute Kidney Injury↗
PubMed1984

Analysis of renal denervation in the hydropenic rat: interactions with angiotensin II.

Nephron filtration rate (SNGFR), its determinants, and proximal tubular reabsorption were measured in hydropenic Munich-Wistar rats with sham-operated (sham) or denervated (DNx) kidneys before and during the administration of [Sar1, Ala8]angiotensin II or SQ 14225. The glomerular ultrafiltration coefficient (LpA) was significantly lower in DNx than in sham rats (P less than 0.025). However, SNGFR was not altered due to an offsetting increment in transcapillary glomerular hydrostatic pressure (delta P) in DNx (P less than 0.005). The marked increment of delta P in DNx was due to an increase in the glomerular capillary hydrostatic pressure, secondary to decreased afferent arteriolar resistance. The infusion of angiotensin II inhibitors to denervated kidneys completely normalized LpA but did not alter sham values. SQ 14225 but not [Sar1, Ala8]angiotensin II infusion provided a nephron plasma flow-dependent increase in SNGFR, secondary to a striking reduction in both glomerular vascular resistances. Endogenous angiotensin II activity may be enhanced by renal denervation, and angiotensin II acts to reduce LpA in this condition and may modulate the final level of renal vascular resistances after acute renal denervation.

Absorption↗
PubMed1985

Fasting induces denervation natriuresis in the conscious rat.

The participation of renal nerves in the regulation of sodium excretion was studied in fed and overnight-fasted rats subjected to acute or chronic left kidney denervation or sham operation. Clearance experiments were performed on conscious restrained animals. Urine flow, glomerular filtration rate (GFR), and urinary sodium excretion were not different in left and right kidneys of sham-operated rats. In fed conscious rats, urine flow, GFR, and urinary sodium excretion of innervated (I) and denervated (D) kidneys were similar. In fasted conscious rats, significant denervation natriuresis was observed after both acute (I, 1.06 +/- 0.27; D, 1.56 +/- 0.40 mumol . min-1 . g-1, P less than 0.05) and chronic (I, 1.55 +/- 0.19; D, 2.20 +/- 0.18 mumol . min-1 . g-1, P less than 0.01) renal sympathectomy, whereas urine flow and GFR in I and D kidneys were not different. Additional experiments revealed that extracellular fluid and plasma volumes of fasted rats were decreased by approximately 10% compared with those of fed animals due to a significant overnight natriuresis and negative water balance. In fed conscious rats, the renal nerves do not seem to participate in the regulation of sodium excretion. The presence of denervation natriuresis in conscious fasted rats suggests that renal nerves are involved in sodium conservation during fasting to maintain extracellular fluid and plasma volume.

Animals↗
PubMed1985

Effect of cutaneous denervation of face and trunk on thermoregulatory responses to cold in rats.

The effect of eliminating afferent input from cutaneous thermoreceptors of the face and trunk on the ability of rats to regulate body temperature in cool environments was studied. Thermoregulatory ability in a cool environment was assessed first in a 25 degrees C environment and then during slow (20 min) and rapid (5 min) reductions of ambient temperature (Ta) to 15 degrees C by monitoring rate of heat production, rectal temperature, and skin temperature on the back, ear, and tail. These measurements were made in four rats while they were intact and during the 2 wk after cutaneous denervation. Rats were found to regulate body temperature well even after the cutaneous nerves of the trunk and face were sectioned. In eight rats the metabolic curve was determined before and 7-10 days after cutaneous denervation. Although the minimal resting metabolic rates did not differ in the two conditions, the lower critical temperature was significantly elevated from 26.8 to 28.9 degrees C and the rate of rise in metabolic rate per degrees celsius decrease in Ta was also significantly higher after cutaneous denervation. It appears that the higher rate of heat production is in compensation for an increase in the rate of heat loss in denervated rats.

Animals↗
PubMed1985

Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep.

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0-5 and 6-13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.

Animals↗