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Regulation of adrenal angiotensin receptor subtypes: a possible mechanism for sympathectomy-induced adrenal hypertrophy.

OBJECTIVE: Previous studies indicate that the adrenal gland plays a compensatory role in the maintenance of blood pressure in chemically sympathectomized rats. However, the mechanisms responsible for compensatory adrenal responses are poorly understood. This study examined the regulation of adrenal growth and type 1 A, 1 B, and type 2 angiotensin II (Ang II) receptor (AT1A, AT1B and AT2) expression in the adrenal gland induced by sympathectomy. METHODS: Five-week-old male Sprague-Dawley rats were treated with either guanethidine (50 mg/kg per day, intraperitoneally) or vehicle for 5 weeks. Norepinephrine and epinephrine levels in the atrium of the heart were measured by high-pressure liquid chromatography. Plasma renin activity was determined by radioimmunoassay. Adrenal AT1 and AT2 receptor density was determined by radioligand binding assay. Adrenal AT1A, AT1B and AT2 mRNA levels were determined by Northern blot analysis. RESULTS: Norepinephrine and epinephrine levels in the atrium of the heart were decreased 86% (P < 0.0001) and 58% (P < 0.05) by guanethidine treatment, respectively. Plasma renin activity was decreased 71% (P< 0.001) in guanethidine-treated rats compared with vehicle. In contrast, the ratio of adrenal to body weight was increased 38% in guanethidine-treated rats compared with vehicle (P< 0.001). Adrenal AT1 and AT2 receptor density was increased by guanethidine treatment (P< 0.05). Adrenal mRNA levels for AT2 (P< 0.001) and AT1A (P< 0.01), but not AT1B (P>0.05), were increased in guanethidine-treated rats compared with vehicle (P< 0.01). There were positive correlations between adrenal weight and AT2 (r = 0.9, P< 0.001) and AT1A (r = 0.6, P< 0.05) but not AT1B (r = - 0.01, P > 0.05) expression. CONCLUSIONS: Impairment of the sympathetic nervous system with guanethidine withdraws the normal stimulation of this system on the circulating renin-angiotensin system, but upregulates the expression of adrenal Ang II receptors. Increased expression of adrenal AT2 and AT1A receptors may play an important role in adaptive adrenal hypertrophy and hormonal responses to sympathectomy.

Adrenal Glands↗

Effect of sympathectomy on ontogeny of small intestinal disaccharidases in the rat.

In the present study the effect of chemical sympathectomy on the development of small intestinal enzymes in the rat was analyzed. Eight doses of guanethidine sulfate were administered subcutaneously every 48 h to 34 newborn rats, starting at birth. The last dose was given at 14 days of age. Twenty-two littermates served as controls. Intestinal lactase, maltase, sucrase, and alkaline phosphatase were determined at 15, 17, 20, 23, and 25 days of age. Sympathectomy was demonstrated by reduction of the number of perikarya in the superior cervical ganglia in treated rats as compared with control rats. A normal developmental pattern of activities of the disaccharidases in the small intestine was observed in both groups. The activity of alkaline phosphatase was significantly lower (p less than 0.01) in the 15- and 17-day-old treated animals.

Animals↗

Sympathectomy for causalgia: experience with military injuries.

BACKGROUND: Causalgia is a rare disease in civilian practice, and most reports regarding causalgia in the literature are from major extended wars. To increase awareness of this syndrome, our wartime experience with this disease is presented. METHODS: The charts of patients with causalgia referred to two university hospitals for treatment from 1985 to 1989 were retrospectively studied. Characteristics of the cause, clinical manifestations, and the response to therapy were evaluated. RESULTS: Among 1,564 patients with peripheral nerve injuries, there were 54 cases (3.4%) of causalgia. All of the patients, except five, were injured in battle by high-velocity bullets or missiles. Upper extremities were involved in 28 patients (52 %) and lower extremities in 26 patients (48%). The most common presenting symptoms were as follows: burning pain, 100%; wet extremity, 100%; cold extremity, 93%; sensitivity to cold, 89%; paresthesia, 78%; and color changes in the extremities, 55%. In 48 patients (89%), pain was relieved by sympathetic block (3 patients had permanent cure). Six patients had no response to the blocks (11%). Of 45 patients who had temporary relief, all underwent sympathectomy. All of these patients had complete relief of symptoms in the immediate postoperative period and for follow-up from 1 to 6 years. CONCLUSION: Causalgia is essentially a war casualty disease. The condition is associated with burning pain, hyperesthesia, and symptoms of sympathetic overactivity. Sympathectomy is effective and the treatment of choice, particularly for patients who respond temporarily to sympathetic blocks.

Adolescent↗

Muscle flaps' triphasic microcirculatory response to sympathectomy and denervation.

Whether sympathectomy and somatic denervation in muscle flaps increased microcirculatory flow in the short or long term, thus producing an effect similar to the delay phenomenon, which increases survival in transferred skin flaps, was determined. The rat cremaster muscle flap model was used for in vivo microscopy. In the left cremasters of 30 Sprague-Dawley rats, the genitofemoral nerve was divided and the proximal vessels were stripped of their adventitia. The muscle was not elevated. In each rat, the contralateral cremaster served as the control. The rats were assigned to one of five groups: no delay before observation, a 24-hour delay, a 48-hour delay, a 7-day delay, or a 14-day delay. After the delay, red blood cell velocity, vessel diameters, number of functional capillaries, and leukocyte-endothelial interactions were measured. Microvessel response to topical vasoactive substances was measured. Immediately after denervation, red blood cell velocity increased transiently (71 percent; p = 0.006). Main arterioles dilated (20 percent; p = 0.02) at 24 hours, and capillary perfusion increased 36 percent (p = 0.001) at 2 weeks. The microvessels had hyperactive responses to all vasoactive agents 2 weeks after denervation. These findings indicate that proximal sympathectomy with somatic denervation leads to a triphasic, dynamic response in the peripheral microcirculation of the cremaster muscle flap. An initial acute hyperadrenergic phase was followed by a nonadrenergic phase, with significant vasodilatation, and a sensitized phase, with increased capillary perfusion and hyperresponsiveness to vasoactive substances. This study shows that with minimal access to the cremaster muscle flap neurovascular pedicle and without changing the blood supply to the flap, significant hemodynamic improvements can be made in the peripheral microcirculation.

Animals↗

Multimodal approach to rapid discharge after endoscopic thoracic sympathectomy.

BACKGROUND: After a large experience (more than 10 years) with bilateral endoscopic thoracic sympathectomy (ETS) surgery on an outpatient basis, we studied prospectively a multimodal approach to rapid discharge patients undergoing this procedure. METHODS: One hundred and seventeen consecutive patients, aged 13-60 years, ASA physical status I or II, undergoing outpatient ETS under general anaesthesia were enrolled in this study. All patients were managed using a predefined multimodal clinical care protocol consisting of a general balanced anaesthesia. Basic demographic information was collected from each patient. Duration of surgery and anaesthesia and times to PACU and home discharge were recorded as well as intraoperative and postoperative complications like nausea and vomiting. RESULTS: Surgery took 41.4 +/- 22.1 min and anaesthesia lasted 63 +/- 21.5 min. Time between induction of anaesthesia and beginning of surgery and end of surgery to extubation was 15.0 +/- 2.0 and 7.2 +/- 3.1 min, respectively. It took 4.9 +/- 1.5 min from extubation to OR discharge. Time from PACU arrival to discharge was 12.8 +/- 6.3 min. Time of hospital stay was 132 +/- 18 min. No patient experienced vomiting and two had nausea, representing an incidence of 1.7%. The only anaesthetic cause for hospital admission was a severe allergic reaction. CONCLUSION: Multimodal management to rapid discharge after ETS surgery did result in a short time to patient discharge. We confirm that endoscopic thoracic sympathectomy can be performed safely on an outpatient basis with brief postoperative hospital care and a low rate of complications.

Adolescent↗

Laparoscopic extraperitoneal lumbar sympathectomy: technique and early results.

A new technique of balloon-assisted laparoscopic lumbar sympathectomy is described and the results of the initial three cases are described. The procedure is technically straightforward and was accomplished without any complications. It should be compared with other techniques of lumbar sympathectomy in comparative trials; however, this early experience is most encouraging.

Adolescent↗

Selective sympathectomy of the liver: a comparison of orthotopic liver transplantation and intraportal 6-hydroxydopamine injection.

1. Tissue noradrenaline (NA) levels correlate well with the extent of sympathetic innervation of that tissue. 2. In this study the distribution of NA throughout the different lobes of the rat liver was studied. The extent of sympathectomy by means of either orthotopic liver transplantation (OLT) (n = 7) or chemical denervation by intraportal administration of 6-hydroxydopamine (6-OH-DA) (n = 8) was examined. 3. In the normally innervated rat liver, NA was homogeneously distributed throughout the organ. Tissue NA was decreased both by OLT (> 99%) and 6-OH-DA (93%) (both P < 0.001 versus control). 4. Samples of the renal cortex and left ventricle were taken as reference tissues. OLT did not result in any change in reference tissue NA, however, 6-OH-DA decreased renal cortex NA by 93% and ventricular NA by 76%, respectively (both P < 0.01 versus OLT). 5. We conclude that OLT causes selective and complete hepatic sympathectomy but that 6-OH-DA causes incomplete denervation of the liver and significant denervation of other organs.

Animals↗

Effect of chemical sympathectomy on (-)-isoprenaline-induced changes in cardiac beta-adrenoceptor subtypes in the guinea-pig and rat.

1. Quantitative autoradiography was used to determine beta-adrenoceptor densities in cardiac regions of guinea-pigs and rats after chemical sympathectomy with 6-hydroxydopamine, and to examine how chemical sympathectomy affected beta-adrenoceptor changes following infusion of (-)-isoprenaline (400 micrograms kg-1 hr-1, 7 days). 2. Seven days after 6-hydroxydopamine (100 mg kg-1, i.v.), cardiac tissue levels of noradrenaline were reduced by 94.0 +/- 3.5% (guinea-pig) and 86.0 +/- 7.0% (rat). The blood pressure increase in rats to tyramine (0.5 mg, i.v.) was reduced from 118 mmHg in controls to 4.4 mmHg in 6-hydroxydopamine-treated animals. 3. There were no changes 7 and 14 days after 6-hydroxydopamine treatment in total, beta 1-and beta 2-adrenoceptor density in the atrioventricular conducting system and atrial and ventricular myocardium in both species. 4. In control animals, (-)-isoprenaline infusion produced selective reductions in beta 2-adrenoceptor density, whilst beta 1-adrenoceptor density remained unchanged. 5. In 6-hydroxydopamine treated guinea-pigs or rats, (-)-isoprenaline infusion caused no change in beta 1-adrenoceptors except in the right bundle branch whilst beta 2-adrenoceptors were reduced in the atrioventricular conducting system (atrioventricular node, bundle of His, right and left bundle branches) and myocardium (interventricular septum and atria). 6. The differential effect of (-)-isoprenaline on beta 1- and beta 2-adrenoceptors is not therefore due to the occupation of beta 1-adrenoceptors by noradrenaline or to prior down-regulation of beta 1-adrenoceptors by noradrenaline, since it persists after depletion of noradrenaline.

Animals↗

Effects of chronic sympathectomy on muscle fibre composition ISO-myosin patterns, protein synthesis and calcium content in canine gracilis muscle.

We have previously reported functional and histological studies in five beagle dogs with unilateral lumbar sympathectomy. Three months later, fatiguability in the gracilis muscles was increased on the denervated sides, and this was associated with an increase in the relative distribution of FT fibres. Biochemical studies now show that these changes were associated with an increase in cytosolic protein without change in DNA content; this is consistent with an increase in cell size. There was a reduction in the proportion of slow myosin light chain isoforms from 50 +/- 7 to 34 +/- 6%. Noradrenaline levels were increased on the denervated sides but this may reflect greater vascularity. Calcium content did not correlate with fibre type but there was a positive relation with both noradrenaline content (r = 0.73; P less than 0.05) and DNA content (r = 0.84; P less than 0.05). It is concluded that sympathectomy induces several biochemical changes in skeletal muscle which constitute a change and increase in fast myosin light chain synthesis and a corresponding fibre type transformation.

Animals↗

Sympathectomy provides evidence of dopamine storage in rat laryngeal nerve paraganglia.

Catecholamine content in the recurrent and superior laryngeal nerves (RLN and SLN) of the rat was analysed by high-performance liquid chromatography after surgical and chemical sympathectomy. Sympathectomy induced by repeated injections of guanethidine did not lead to any change in the dopamine (DA) level, whereas the noradrenaline (NA) content decreased by 68% and 64% respectively in the RLN and SLN. Surgical excision of the superior cervical ganglion (SCG) did not alter the level of DA in the SLN, but caused a 60% decrease of DA in the RLN. Removal of SCG did not affect the NA levels either in the RLN or in the SLN, unless it was combined with extirpation of the middle cervical ganglion, which induced a decrease in NA in both nerves. The results indicate that much of the DA in the laryngeal nerves is stored outside the sympathetic nerve fibres, probably in the small organs earlier characterized as endoneurial paraganglia.

Animals↗

An assessment of the cardiovascular sympathectomy induced by guanethidine.

Guanethidine treatment of rate (30 mg kg(-1), i.p. daily for 6 weeks) produced a profound reduction in the catecholamine present (as indicated by fluorescence histochemistry and catecholamine determinations) in tissues taken from the cardiovascular system, but there was evidence of the return of catecholamines within 8 weeks. While these changes are consistent with a sympathectomy, the unaltered pressor responses to physostigmine (100 mug kg(-1), i.v.) and to carotid occlusion indicate an unimpaired functional capacity of noradrenergic nerves supplying the cardiovascular system. Although part of the response may be attributed to the unaffected adrenal medulla enhanced by the presence of considerable supersensitivity as shown to exogenous noradrenaline, there would appear to be a dissociation between the results obtained from physical and functional tests of the sympathectomy induced by guanethidine.

Animals↗

Secretion of parotid acinar granules in rats during reflex stimulation after chronic sympathectomy.

After chronic post-ganglionic sympathectomy the ultrastructure of 'resting' parotid acinar cells in rats remains relatively normal, despite the loss of nerve impulses normally causing secretion of acinar granules from this gland. The question whether eating hard chow still induces some acinar degranulation weeks after superior cervical ganglionectomy, has now been tested. It was found that scattered pockets of parotid acinar degranulation did occur. Some of these changes after unilateral denervation may have been attributable to intact sympathetic nerves arising from the contralateral superior cervical ganglion (Alm, Asking, Emmelin & Gjörstrup, 1984), but this cannot explain similar changes that occurred in glands after bilateral ganglionectomy. The possibility that some degranulation may be induced by circulating catecholamines was tested, 9-16 weeks after unilateral sympathectomy, by placing animals in the cold (0-4 degrees C) for 2 h before removal of tissues. Animals not given food during that time showed no evidence of parotid acinar degranulation, but those given hard chow showed extensive acinar degranulation in both parotid glands. On the sympathectomized side the degranulation was, however, less uniform and more patchy than on the side with an intact innervation. These findings agree with he belief that circulating catecholamines can, at times, induce degranulation of parotid acinar cells made supersensitive by chronic sympathetic denervation but, for it to occur, the cells must also be receiving parasympathetic stimulation at the same time. This interaction probably permits a sufficient turnover of granules to maintain a relative homoeostasis of the parotid acinar cells in rats.

Animals↗

Thoracoscopic sympathectomy for palmar hyperhidrosis and Raynaud's phenomenon of the upper limb and excessive facial blushing: a five year experience.

Primary hyperhidrosis of the palms, face, and axillae has a strong negative impact on social and professional life. A retrospective analysis of 40 laparoscopic transaxillary thoracic sympathectomies performed in a district general hospital over a five year period was undertaken in order to determine the effectiveness of this procedure. A postal questionnaire was sent to all patients to assess the benefit from the operation; postoperative pain and time off work were collated. Immediate failure was noted in three patients, of whom two later underwent successful reoperation. Recurrence was noted in three patients (8%). Though immediate complications were minimal, the major long term postoperative morbidity was compensatory hyperhidrosis on the back, chest, and thigh (77%) along with gustatory sweating over the face (22%). Thoracoscopic sympathectomy is a safe, effective, and minimally invasive surgical treatment for hyperhidrosis, Raynaud's phenomenon of the upper limb, and excessive facial blushing; however, the chance of long term compensatory hyperhidrosis is high.

Adolescent↗

Effect of sympathectomy on inotropic responsiveness to alpha-adrenoceptor stimulation in developing mouse myocardia.

Effects of postnatal sympathectomy on inotropic responsiveness to alpha-adrenoceptor stimulation were examined in mouse myocardia to determine whether the developmental conversion of alpha-adrenoceptor-mediated inotropic responses from positive to negative is triggered by sympathetic innervation. Sympathectomy was performed chemically by consecutively administering 6-hydroxydopamine for 14 days after birth and confirmed by the absence of inotropic responses to tyramine. In newborn myocardia, phenylephrine, in the presence of propranolol, produced concentration-dependent positive inotropic responses. Three weeks after birth, phenylephrine, in the presence of propranolol, produced concentration-dependent negative inotropic responses, both in control and in sympathectomized myocardia; no difference was observed between the two groups of mice in the maximum decrease in contractile force produced by phenylephrine. The sensitivity (pD2 value) to phenylephrine was significantly higher in sympathectomized myocardia. In conclusion, sympathetic innervation of the mouse ventricular myocardium is not required for the developmental conversion of the alpha-adrenoceptor-mediated inotropic response from positive to negative.

Adrenergic alpha-Agonists↗

Compensatory adrenal cortical growth is inhibited by sympathectomy.

After the surgical removal of one adrenal gland, the cortex of the remaining adrenal gland increases in size. This compensatory adrenal growth is characterized by increased weight and DNA content of the remaining adrenal 72 h after unilateral adrenalectomy. In these experiments, chemical sympathectomy prevented compensatory adrenal growth. In rats sympathectomized by neonatal injections of 6-hydroxydopamine or guanethidine and unilaterally adrenalectomized at 40 days of age, the compensatory increase in weight in the remaining gland was attenuated (relative to a vehicle-injected control group) and not accompanied by the usual increase in DNA content. Augmented RNA content was observed after unilateral adrenalectomy in sympathectomized as well as vehicle-injected animals; presumably this reflects increased steroidogenesis because, despite the loss of one adrenal, the rats maintained normal plasma corticosterone and aldosterone levels (relative to the sham-adrenalectomized group). The sympathectomy procedures themselves did not significantly alter adrenal weight, adrenal nucleic acid content, or plasma aldosterone relative to vehicle-injected control levels; however, plasma corticosterone levels were significantly reduced. We conclude that the sympathetic nervous system mediates the adrenal cortical cell proliferation that occurs after unilateral adrenalectomy.

Adrenal Cortex↗

Effects of sympathectomy on blood pressure and its variability in conscious rats.

To further assess the role of the sympathetic nervous system (SNS) in the control of blood pressure (BP), continuous recordings of BP were performed in conscious freely moving rats that had received daily injections of guanethidine or saline from 7 to 90 days of age. Guanethidine extensively destroyed the peripheral sympathetic fibers as indicated by marked decreases in the norepinephrine content of the heart and kidneys and the absence of pressor response to tyramine injection. Such a chronic sympathectomy did not alter the BP and heart rate (HR) levels but markedly enhanced the BP variability while the HR variability and the sensitivity of the cardiac baroreceptor reflex were not altered. Angiotensin-converting enzyme inhibition with perindopril induced a rapid fall in BP and normalized the BP variability in sympathectomized animals. It is concluded that in rats, the SNS is not necessary for the full development of the BP level but is essential to buffer the spontaneous variability of BP. After sympathectomy, BP is maintained at nearly normal levels mainly through activation of the renin angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of adrenalectomy or sympathectomy on spinal cord blood flow in hypothermic rats.

We used [14C]butanol distribution to measure regional spinal cord blood flow (RSCBF) in three groups of pentobarbital-anesthetized rats: 1) normals (n = 16); 2) after bilateral adrenalectomy (n = 18); and 3) after excision of the abdominal sympathetic chains (n = 12). Half of the rats in each group were maintained near normothermia; the remainder were colled to a rectal temperature of 25-27 degrees C. In intact rats, there was a 24-37% increase in RSCBF during hypothermia in the cord region C3-L6 inclusive. Neither operative procedure altered RSCBF during normothermia. In hypothermic adrenalectomized rats, RSCBF was elevated only in the C3-C5 cord segment. After sympathectomy, RSCBF was unchanged during hypothermia. In the cauda equina, flow fell in all hypothermic rats. The hypothermia-associated increases in RSCBF were not related to changes in mean arterial blood pressure. We conclude that adrenalectomy near-totally ablates the hypothermia-associated increase in RSCBF measured in intact rats and that abdominal sympathectomy totally ablates it. This evidence complements morphological evidence for adrenergic innervation of the spinal cord vasculature.

Adrenalectomy↗

Sympathectomy exaggerates antihypertensive effect of vasopressin withdrawal.

The role of sympathetic function in the mechanism of the decrease in arterial pressure that follows withdrawal of an intravenous infusion of arginine vasopressin (AVP) in spontaneously hypertensive rats (SHR) was studied by comparing this withdrawal-induced antihypertensive phenomenon (WAP) in rats with intact sympathetic function to those subjected to sympathectomy. Sympathectomy with guanethidine did not lower blood pressure significantly in either SHR or normotensive Wistar-Kyoto (WKY) rats despite a marked impairment of sympathetic function as judged by a dramatic attenuation of blood pressure responses to tyramine and by evidence of denervation supersensitivity to phenylephrine. Cessation of a 3-h intravenous infusion of AVP (20 ng.kg-1.min-1) was associated with large and prolonged decrease in pressure below preinfusion levels in SHR with intact sympathetic function: 5 h after stopping the infusion, pressure was 27 +/- 3 mmHg below preinfusion levels. In sympathectomized SHR, the decrease in pressure after cessation of the AVP infusion was much larger: 5 h after the infusion, pressure was 44 +/- 2 mmHg below preinfusion levels. In contrast to SHR, pressure returned to control levels in WKY with intact sympathetic function after withdrawal of AVP. A small but significant decrease in pressure occurred after withdrawal of AVP in sympathectomized WKY. The results are consistent with the hypothesis that withdrawal of sympathetic activity is a contributing factor or a prerequisite condition for development of a WAP.

Animals↗