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Trophic effect of the sympathetic nervous system on vascular smooth muscle.

While the vasomotor effect of the sympathetic nervous system (SNS) on the arterial wall is well recognized, its trophic function is not. It is the aim of these studies to demonstrate this all-important function as it relates to the vascular muscle. Although the exact mechanism by which sympathetic nerve impulses influence the metabolism of the vessel wall is unknown, effects of sympathectomy can be demonstrated. Several lines of evidence indicate that chronic absence of sympathetic innervation in rabbits increases collagen synthesis and decreases activity of tricarboxylic acid cycle enzymes in the vascular wall. When chemically sympathectomized rabbits were fed a 1% cholesterol dietary supplement for 80 days, the aortas of these rabbits contained significantly more cholesterol and total lipids than those from fully innervated controls in spite of insignificant differences in plasma lipids. In a subsequent series of experiments we analyzed the efficacy of the SNS in two strains of pigeons. White Carneau (WC) pigeons are known by the susceptibility to atherosclerosis of the aorta while Show Racer (SR) pigeons are not. Our results demonstrate that the abdominal aorta of WC pigeons has less sympathetic innervation and it declines faster with age than that of SR pigeons. The results of the described studies documenting the direct trophic influence of the SNS on the arterial wall are reinforced by the similarity to the vessel wall changes induced by partial sympathectomy and natural ageing.

Acetylglucosaminidase↗

Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT.

UNLABELLED: The 11C-labeled tracer meta-hydroxyephedrine (11C-HED) is a noradrenaline analog that was developed to visualize the sympathetic nervous system with PET. Initial clinical studies show a rapid uptake of 11C-HED in localized tumors of this system. Whole-body imaging with 11C-HED PET is now possible as PET/CT scanners allow a rather short examination time. The aim of this study was to evaluate the feasibility of whole-body 11C-HED PET/CT for examination of tumors of the sympathetic nervous system and to directly compare the results with 123I-labeled meta-iodobenzylguanidine (123I-MIBG) scintigraphy, including SPECT/CT. METHODS: In 19 consecutive patients, 9 mo to 68 y old (median, 32 y), 24 whole-body 11C-HED PET/CT (low-dose CT) examinations were performed. Scans were compared with attenuation-corrected 123I-MIBG SPECT/CT scans (24-h scan, low-dose CT). The intensity of tracer accumulation above background was visually analyzed in both scans, PET and SPECT, using a 4-value scale. In 11C-HED PET, mean and maximum standardized uptake values were determined for all lesions. RESULTS: In 14 patients with 19 pairs of examinations, the following tumors were confirmed histologically: 6 neuroblastomas, 5 pheochromocytomas, 1 ganglioneuroblastoma, and 2 paragangliomas. In 5 patients, each having 1 pair of examinations, clinical follow-up and/or histologic examination did not reveal any tumor deriving from the sympathetic nervous system. 11C-HED PET/CT detected 80 of 81 totally depicted tumor lesions (sensitivity, 0.99; soft tissue, 61; bone, 19). 123I-MIBG SPECT/CT detected 75 of 81 lesions (sensitivity, 0.93; soft tissue, 56; bone, 19). With both methods, there were no false-positive lesions. The tumor-to-background contrast of 11C-HED uptake was higher in comparison with 123I-MIBG uptake in 26 lesions (0.32; soft tissue, 18; bone, 8), equal in 39 lesions (0.48; soft tissue, 30; bone, 9), and lower than 123I-MIBG uptake in 16 lesions (0.20; soft tissue, 14; bone, 2). CONCLUSION: Whole-body imaging using 11C-HED PET/CT is feasible in the clinical setting of patients with tumors of the sympathetic nervous system. 11C-HED PET/CT detected more tumor lesions than 123I-MIBG SPECT/CT. However, tumor-to-background contrast of 11C-HED in lesions can be higher, equal, or lower compared with 123I-MIBG.

3-Iodobenzylguanidine↗

[Interaction between SR 47436, a new angiotensin II antagonist and sympathetic nervous system in pithed SHR rats].

In vivo studies have previously shown that exogenous angiotensin II (AII) reinforces sympathetic nervous system activity. Conversely, non selective inhibition of endogenous AII by angiotensin I converting enzyme inhibitors (ACEIs) results in sympathoinhibitory effects. The aim of the present study was to examine the influence of selective inhibition of endogenous AII by SR 47436, a non peptide AT1-receptor antagonist, on the sympathetic nervous system. Cardiac, systemic and regional vascular (kidney, mesentery, hindlimb) responses to selective alpha 1- and alpha 2-adrenoceptor agonists and to electrical stimulation of the spinal cord were investigated in the pithed spontaneously hypertensive rat (SHR). Male adults SHRs were orally treated by SR 47436 (10 mg/kg/day for 8 days) or by distilled water. Two hours later, they were anesthetized with pentobarbital (50 mg/kg, i.p.), pithed and artificially ventilated. Blood pressure, heart rate, cardiac output and regional (kidney, mesentery and hindlimb) blood flows (pulsed Doppler technique) were measured. Corresponding vascular resistances were calculated. Three hours after SR 47436--at the time of the drug's maximal effects--or distilled water administration, cardiac, systemic pressor and regional vasoconstrictor responses (a) to increasing i.v. doses of AII, (b) to increasing frequencies of electrical stimulation of the spinal cord, and (c) to increasing i.v. doses of cirazoline, a selective alpha 1-adrenoceptor agonist, and of UK-14,304, a selective alpha 2-adrenoceptor agonist, were investigated. AII systemic pressor, regional vasoconstrictor and tachycardic responses were completely abolished by SR 47436. SR 47436 significantly reduced the systemic pressor responses elicited by spinal cord stimulation, cirazoline and UK-14,304.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

The sympathetic nervous system and long-term regulation of arterial pressure: what are the critical questions?

1. The role of the sympathetic nervous system in long-term control of arterial pressure remains unclear despite decades of intense research. 2. Previous studies have shown that denervation of arterial baroreceptors does not chronically increase arterial pressure. As baroreceptors are thought to provide the primary 'error signal' to the autonomic nervous system, this has been interpreted as evidence against neural control of arterial pressure over long periods of time. 3. The possibility that other 'error signals' are important in the long-term control of sympathetic activity (and arterial pressure) is introduced. 4. The following 'Critical Questions' are presented for subsequent discussion: (i) is the sympathetic nervous system a 'major player' in the long-term control of arterial pressure; (ii) why doesn't arterial pressure remain at hypertensive levels after arterial baroreceptor denervation; and (iii) which 'error signals' are most important in the long-term control of sympathetic outflow?

Animals↗

Is the sympathetic nervous system altered in children with familial history of arterial hypertension?

The sympathetic nervous system has been investigated in 42 children with family history of arterial hypertension and 68 children of the same age without hypertensive relatives. Pressure responses to mental arithmetic and to isometric handgrip stress were measured in both groups, along with 24 h catecholamine excretion. Resting blood pressure and heart rate did not show any difference between groups. The increase in diastolic pressure during the mental arithmetic exercise was, however, significantly greater in children with family history of hypertension. A sharp increase in blood pressure and heart rate was observed during isometric handgrip in both groups without any significant difference. Twenty-four hour catecholamine urinary excretion was significantly higher in the group with family history of hypertension (31 +/- 15 vs. 23 +/- 13 micrograms/24 h; p less than 0.05). These results seem to indicate that an initial impairment of the sympathetic activity is already detectable in young offspring of hypertensive patients.

Blood Pressure↗

Inhibition of sympathetic nervous system by acupuncture.

The central and peripheral sympathetic activities were measured both physiologically and biochemically in either human subjects or conscious rabbits. Acupuncture reduced NE levels in perfusates of certain brain areas as well as in blood circulation, accompanied with a rise of pain threshold, and changes of certain physiological indices (palm temperature, fingerplethysmogram and pain tolerance threshold) which are related with functions of sympathetic nervous system. These results suggest that the NE neurons of NE ascending dorsal fasciculus has some antagonizing effect on acupuncture analgesic effect, acupuncture inhibits sympathetic activities, and such inhibition plays a favorable role in acupuncture analgesia.

Acupuncture Therapy↗

The relationship between the sympathetic nervous system and the renin-angiotensin system in renovascular hypertension.

UNLABELLED: The aim of this study is to evaluate and compare the activity of the sympathetic nervous system and the renin-angiotensin system in patients with unilateral or bilateral renovascular hypertension. Plasma noradrenaline (plNA) levels and plasma renin activity (PRA) were measured simultaneously in blood samples obtained both from a peripheral vein and from the renal veins, during catheterization of the venous cava system, in 17 patients with unilateral (group A) and in 9 patients with bilateral renal artery stenoses (group B). RESULTS: peripheral plNA levels were elevated in 6/17 patients of the group A and 3/9 patients of the group B, while in the remaining 11/17 and 6/9 were normal, respectively. The comparison of plNA levels between the renal veins showed that in both groups plNA levels were higher in the renal vein of the ischaemic (group A) or the more ischaemic kidney (group B), and the difference was statistically significant. Renal vein renin ratio was above 1.5 in both groups. Renin hypersecretion from the ischaemic or the more ischaemic kidney compared to renin suppression from the normal or the less ischaemic kidney showed statistically significant difference.

Humans↗

Ketamine acts on the peripheral sympathetic nervous system of guinea pigs.

The effects of ketamine on the peripheral sympathetic nervous system were studied in vitro by observing the amplitude of the nerve-mediated contraction of the vasa deferentia isolated from guinea pigs. Ketamine dissolved in the perfusate of an organ bath was applied to the tissues for 30 minutes and then washed out with a perfusate lacking ketamine for 90 minutes. Ketamine in concentrations of 10(-8) and 10(-7) g/ml had no effect on contraction induced by hypogastric nerve (preganglionic) stimulation. At 10(-6) g/ml, the drug had no significant effect during application but was associated with increased contractions during washout. At 10(-5) and 10(-4) g/ml, the drug showed a dose-related depression during application and an increase in contractions during washout after a 10(-5) g/ml. Ketamine, 10(-5) g/ml, increased contraction following transmural (postganglionic) stimulation and had a depressant effect at a concentration of 10(-4) g/ml. It is concluded (1) that ketamine has dual effects on the nerve-mediated contraction of the vasa defentia and (2) that cardiovascular responses to ketamine include peripheral effects of ketamine on sympathetic ganglia.

Animals↗

The role of the sympathetic nervous system in linking obesity with hypertension in white versus black Americans.

Several previous studies confirmed that obesity is a major risk factor for the development of cardiovascular diseases, including hypertension. A large number of clinical studies considered the role of the sympathetic nervous system in linking obesity with hypertension, and there is substantial evidence that human obesity is characterized by defects in sympathetic cardiovascular control. The association of obesity with hypertension has been well documented in most racial, ethnic, and socioeconomic groups. Ethnicity may be an important factor to consider since sympathetic nervous system activity, and the propensity for obesity and hypertension, all differ substantially among different populations. Obesity is actually accompanied by increased sympathetic nerve discharge to skeletal muscles, a main site for energy expenditure. Adiposity-related sympathetic overactivity is a compensatory mechanism to burn fat and decrease weight gain, but at the cost of increased sympathetic discharge to the peripheral vasculature, which could predispose to hypertension. Thus, sympathetic nervous system activity is important in the development and maintenance of obesity-related hypertension in different racial and ethnic populations, including white and black Americans.

Black People↗

Responses of sympathetic nervous system to cold exposure in vibration syndrome subjects and age-matched healthy controls.

Plasma norepinephrine and epinephrine in vibration syndrome subjects and age-matched healthy controls were measured for the purpose of estimating the responsibility of the sympathetic nervous system to cold exposure. In preliminary experiment, it was confirmed that cold air exposure of the whole body was more suitable than one-hand immersion in cold water. In the main experiment, 195 subjects were examined. Sixty-five subjects had vibration syndrome with vibration-induced white finger (VWF + group) and 65 subjects had vibration syndrome without VWF (VWF- group) and 65 controls had no symptoms (control group). In the three groups, plasma norepinephrine levels increased during cold air exposure of whole body at 7 degrees +/- 1.5 degrees C. Blood pressure increased and skin temperature decreased during cold exposure. Percent increase of norepinephrine in the VWF+ group was the highest while that in VWF- group followed and that in the control group was the lowest. This whole-body response of the sympathetic nervous system to cold conditions reflected the VWF which are characteristic symptoms of vibration syndrome. Excluding the effects of shivering and a cold feeling under cold conditions, it was confirmed that the sympathetic nervous system in vibration syndrome is activated more than in the controls. These results suggest that vibration exposure to hand and arm affects the sympathetic nervous system.

Adult↗

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↗

Effects of the dopaminergic agonist cianergoline on blood pressure, the renin-angiotensin-aldosterone axis and the sympathetic nervous system in patients with essential hypertension.

Cianergoline is a new dopaminergic agonist with a predominant cardiovascular action. Its effects on blood pressure, the renin-angiotensin-aldosterone axis, the sympathetic nervous system and lipid metabolism were assessed in 20 patients with benign essential hypertension. Cianergoline given in increasing doses for 4 weeks (maximum daily dose 12 +/- 2 mg (SD)) and placebo both caused a slight decrease in arterial pressure, (from 159/104 to 152/98 mm Hg and from 154/104 to 149/103 mm, respectively; difference not significant). Supine and upright plasma renin activity, plasma aldosterone, norepinephrine, epinephrine and dopamine levels, urinary catecholamine excretion rates as well as serum prolactin, low and high density cholesterol and triglyceride concentrations were not changed after cianergoline or placebo. Total serum cholesterol and triglyceride levels decreased significantly after placebo, but were unchanged after cianergoline. 3 out of 10 patients in the cianergoline group complained of nausea. The findings indicate that the new dopaminergic agonist cianergoline exerts only a mild blood pressure lowering effect in patients with essential hypertension and does not modify the release of prolactin, lipid metabolism or the basal activity or postural responsiveness of the renin-angiotensin-aldosterone axis and of the sympathetic nervous system.

Adult↗

Contribution of the sympathetic nervous system to vascular resistance in conscious young and adult spontaneously hypertensive rats.

Although evidence exists for exaggerated sympathetic nervous system activity in spontaneously hypertensive rats (SHR), there are no studies in conscious animals that directly demonstrate that this increased activity is functionally involved in the elevated vascular resistance of these animals. In our present study, 8-week-old and 13-week-old SHR and Wistar Kyoto controls (WKY) were chronically instrumented with arterial and venous catheters and miniaturized pulsed Doppler flow probes on the renal and mesenteric arteries and lower abdominal aorta. While the rats were conscious and unrestrained, hexamethonium was administered intravenously to block sympathetic nervous system transmission. Prior to hexamethonium, the mean arterial pressure of young SHR and WKY averaged 123 plus or minus 5 and 109 plus or minus 4 mm Hg respectively (p smaller than 0.05), while adult SHR and WKY averaged 159 plus or minus 7 and 128 plus or minus 3 mm Hg respectively (p smaller than 0.05). Hexamethonium produced an equivalent fall in arterial pressure of young SHR (-32%) and WKY (-30%) and adult SHR (-39%) and WKY (-41%). Vascular resistance was reduced by hexamethonium in the kidney, gut, and hindquarters, but the percent changes were not significant between SHR and WKY. These data suggest that, in both young and adult SHR, vascular resistance and arterial pressure are sustained at elevated levels by some other mechanism than neurally-derived vasoconstrictor tone.

Angiotensin II↗

[The sympathetic nervous system activity estimated on serum concentration of chromogranin A in patients with the chronic heart failure].

BACKGROUND: The sympathetic nervous system is markedly activated in patients with chronic heart disease. This activation can be evaluated by assessing the serum levels of chromogranin A (CgA), the protein which is present in the all neuroendocrine cells. The main human source of CgA are adrenal medullary and sympathetic nerve endings. The aim of the study was to demonstrate if serum concentration of chromogranin A correlated to severity of chronic heart failure and it can be usefulness for clinical diagnosis. MATERIAL AND METHODS: The serum levels of CgA were measured in 123 patients. Patients with chronic heart disease (n = 100) were divided into four groups depending of the severity of heart failure--NYHA classification (B1--NYHA I, B2--NYHA II, B3--NYHA III, B4--NYHA IV). The control group consisted of 23 persons without heart disease. The patients in both groups were examined and had performed tests: electrocardiography, echocardiography, blood morphology and the blood concentrations of creatinine, glucose, electrolytes, lipids. The serum concentration of chromogranin A was assessed by specific and immunoenzymatic sandwich ELISA test. RESULTS: The mean serum concentration of CgA in the control group was 48.43 +/- 2.97 micrograms/L. In the chronic heart disease group the concentrations of CoA increased with the degree of NYHA heart failure and in four groups (B1, B2, B3, B4) the CgA levels were: 42.10 +/- 19.52; 49.84 +/- 22.63; 73.64 +/- 34.08; 106.66 +/- 87.54 micrograms/L respectively. The concentrations in groups B3 and B4 were significantly higher than in control group. The LV ejection fraction was reduced in groups B1-B4 (mean +/- SD): 60.12 +/- 9.20; 47.45 +/- 11.10; 40.28 +/- 9.52%. The CgA concentration was significantly negatively correlated with LV ejection fraction (r = -28). The left atrium was in group B1-B4:--32.94 +/- 4.35, 38.73 +/- 7.87, 42.57 +/- 7.98, 46.32 +/- 10.67 mm. The heart rate rised with the NYHA class (the control group (mean +/- SD): 72.96 +/- 9.15/min) and in the groups B1-B4 (mean +/- SD): 78.15 +/- 14.35, 79.90 +/- 14.67; 85.40 +/- 14.11; 93.74 +/- 16.29/min. The heart rate was significantly higher in B3 and B4 groups. CONCLUSIONS: 1. The serum concentrations of chromogranin A were correlated with the severity of chronic heart failure based on NYHA classification. 2. The CgA concentrations were significantly negatively correlated with the LV ejection fraction. 3. The chromogranin A can be used as a marker of the sympathetic nervous system activation in the patients with chronic heart failure.

Adult↗

[The participation of the sympathetic nervous system in thromboxane A2 release induced by limb ischemia].

Our previous studies indicate that the blockade of the sympathetic nervous system by spinal anesthesia or epidural anesthesia inhibits the release of TXA2 induced by limb ischemia with thigh tourniquet in patients with lower limb surgery. The present study was undertaken to confirm this phenomenon in anesthetized dogs. Twenty one anesthetized dogs underwent 60 min occlusion of the abdominal aorta and the inferior vena cava, followed by reperfusion. They were randomized into three groups: no treatment group and pretreatment groups with either 2 ml of 0.5% bupivacaine intrathecally or 4 mg.kg-1 of labetalol intravenously. In no treatment group plasma TXB2 levels were increased significantly after reperfusion. However, prior treatments with bupivacaine intrathecally or labetalol intravenously inhibited the increases in plasma TXB2 levels after reperfusion. These results suggest that limb ischemia stimulates the TXA2 production, which may be influenced not only by endothelial cell damage and the generation of oxygen free radicals but also by the activation of the sympathetic nervous system.

Animals↗