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PubMed1983

Effect of dietary fat on sympathetic nervous system activity in the rat.

Previous studies from our laboratory have demonstrated that dietary intake affects the sympathetic nervous system (SNS); carbohydrate intake, in particular, has been shown to stimulate sympathetic activity. The present studies were undertaken to characterize the effect of dietary fat on SNS activity in the rat. Sympathetic activity was assessed by measurement of norepinephrine (NE) turnover in heart, interscapular brown adipose tissue (IBAT), and pancreas and by excretion of NE in the urine. When fed a fat-enriched diet (50% chow, 50% lard), fractional NE turnover in heart (k) increased from 6.3 +/- 0.6% h in ad lib. fed controls to 14.7 +/- 1.3% h in the high-fat group (P less than 0.001); calculated NE turnover rate increased from 24.5 +/- 2.4 ng/heart per h to 36.8 +/- 3.5 (P less than 0.05). Urinary NE excretion more than doubled after 6 d of the same high fat diet (P less than 0.001). Ganglionic blockade produced a greater effect on NE turnover in fat-fed, as compared with chow-fed animals, consistent with increased sympathetic activity in the fat-fed group. When fat absorption was blocked with a bile acid binding resin (cholestyramine), the same high-fat diet did not increase cardiac NE turnover, indicating that fat absorption is required for the stimulatory effect on sympathetic activity. In another series of experiments, in which chow (and hence protein) intake was held constant, the effect of fat and isocaloric sucrose supplements on NE turnover was assessed in heart, IBAT, and pancreas. The caloric value of the supplements was 50, 100, and 335% of the chow in the different experiments. An effect of fat on NE turnover in heart and IBAT was demonstrable at the lowest level of fat supplement. Fat increased pancreatic NE turnover when added in amounts sufficient to double the caloric intake. The stimulatory effect of sucrose and fat on NE turnover in heart and IBAT was similar. These experiments demonstrate that fat increases SNS activity in the rat and that the magnitude of the effect is similar to that of sucrose. The results imply that fat may contribute to dietary thermogenesis in this species.

Adipose Tissue, Brown↗
PubMed1998

Measurement and prediction of sympathetic nervous system activity in humans.

The measurement of norepinephrine (NE) kinetics has broadened our understanding of sympathetic nervous system activity involvement in energy expenditure, blood pressure regulation and substrate utilization. This methodology, however, has several disadvantages that include administration of radioactivity to volunteers, its expense, and time consuming laboratory analyses. Thus, we developed an equation to predict plasma NE appearance rate (NEAP) derived from infusions of tritiated norepinephrine performed in 113 healthy men (18-78 yr.). The accuracy of the equation was tested using cross-validation procedures. Age, fat mass, plasma [NE], waist circumference, and body weight (BW) correlated significantly with plasma NE appearance rate. The resulting prediction equation in the validation group was: NEAP = 0.00003148 BW [NE], with R2 = 0.76 and was successfully cross-validated. Using pooled data from both groups the prediction equation was: NEAP (microg/min) = 0.00003108 x [NE (pg/ml)] x [Body weight (kg)] with an R2 = 0.70 and SEE = 0.096 microg/min. The magnitude of error associated with this equation allows for detection of age-associated, exercise-induced changes and blood pressure-related differences in plasma NE appearance rate published in the literature. We provide an equation that offers a relatively simple and accurate alternative to estimate plasma NE appearance from the measurement of arterialized plasma [NE] and body weight.

Adolescent↗
PubMed1977

Agreement among three different indices of sympathetic nervous system activity in essential hypertension.

Although plasma norepinephrine concentration often is elevated in patients with essential hypertension, the relevance of this to the pathogenesis of the blood pressure elevation remains uncertain. If the high concentration of plasma norepinephrine truly indicates sympathetic nervous system overactivity, it should be accompanied by hemodynamic features suggestive of sympathetic cardiovascular stimulation. This proposition was tested, and in part confirmed, in a study performed on 21 patients who had mild essential hypertension and on 11 normal subjects. Among hypertensive patients, plasma norepinephrine concentration was related to cardiac function but not to the level of the blood pressure or to total peripheral vascular resistance. Plasma norepinephrine concentration correlated significantly with heart rate and cardiac preejection period index at rest and with changes in cardiac output, heart rate, and preejection period after cardiac beta-adrenergic blockade produced by propranolol, 0.2 mg/kg intravenously. Patients with an elevated plasma norepinephrine concentrations (9 of 21) showed features of sympathetic cardiac stimulation, manifested by an elevated mean cardiac index and heart rate at rest and by normalization of both after treatment with propranolol. Thus, substantial agreement existed among three commonly used indices of sympathetic nervous system activity--plasma norepinephrine concentration, general hemodynamics at rest, and the hemodynamic response to pharmacologic autonomic blockade.

Adolescent↗
PubMed1999

Brain-IL-1beta induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system.

It is well established that systemic inflammation induces a counter-regulatory anti-inflammatory response particularly resulting in deactivation of monocytes/macrophages. However, recently we demonstrated a systemic anti-inflammatory response without preceding signs of systemic inflammation in patients with brain injury/surgery and release of cytokines into the cerebrospinal fluid (CSF). In order to analyze the mechanisms and pathways of systemic immunodepression resulting from sterile cerebral inflammation we established an animal model using continuous intra-cerebroventricular (i.c.v.) or intra-hypothalamic (i.h.) infusion of rat recombinant (rr) tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta for 48 h. Controls received intra-venous (i.v.) cytokine administration. Interestingly, i.c.v. and i.h. infusion of IL-1beta but not TNF-alpha produced distinct signs of central nervous system (CNS) inflammation. Correspondingly, i.c.v. infusion of IL-1beta particularly diminished the TNF-alpha but increased the IL-10 concentration in whole blood cultures after endotoxin stimulation. All parameters normalized within 48 h after termination of the infusion. Blocking the hypothalamic-pituitary-adrenal (HPA) axis by hypophysectomy (HPX) led to complete recovery of the diminished TNF-alpha concentration and temporarily inhibited the IL-10 increase. Blocking the sympathetic nervous system (SNS) transmission by application of the beta2-adrenoreceptor antagonist propranolol not only inhibited the increase but further downregulated the endotoxin induced IL-10 concentration in the media of whole blood cell cultures, whereas the TNF-alpha decrease was only partially prevented. Interestingly, HPX and propranolol also diminished the cell invasion into the CSF. In summary, activation of both the HPA axis and the SNS plays an important role in systemic anti-inflammatory response resulting from cytokines in brain and cerebral inflammation.

Animals↗
PubMed1986

Functional plasticity in the sympathetic nervous system of the neonatal rat.

The age-dependent effects of sympathetic superior cervical ganglionectomy on smooth muscle alpha-adrenoceptor contractile responses were investigated in Müller's muscle in the superior eyelid of the Sprague-Dawley rat. Ganglionectomies in juvenile (32 days) and adult (70 days) rats produced sustained sympathetic denervation, determined by absence of contractile responses to electrical stimulation of ipsilateral and contralateral sympathetic chains and reduced responses to indirect release of nerve terminal norepinephrine by tyramine. Denervation was associated with diminished contractile responses and postjunctional supersensitivity to alpha-adrenoceptor stimulation by methoxamine. In contrast, contractile responses in rats ganglionectomized as neonates (day 3) were greater than those of other groups and sensitivity to methoxamine was comparable to control values. Responses to tyramine suggested that noradrenergic reinnervation had occurred. Electrical stimulation of the ipsilateral chain did not elicit contractions; however, stimulation of the contralateral chain evoked contractions in all neonatally ganglionectomized preparations and responses were present by 20 days of age. Contralateral reinnervation was derived from postganglionic sympathetic neurons with axons in the internal carotid nerve. This pathway is probably not formed by collateral sprouting of neurons with bilateral projections at the time of surgery for contralateral stimulation did not evoke contractions in the neonate. It is concluded that Müller's muscle is reinnervated by sympathetic neurons in the contralateral chain after denervation in neonates but not in older animals, and it is suggested that the higher potential for plasticity is attributable to the immaturity of the neonatal sympathetic nervous system.

Animals↗
PubMed1986

Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses.

Increased energy intake activates the sympathetic nervous system (SNS) in animals and man. While dietary carbohydrate and fat stimulate, the impact of dietary protein on the SNS is not well defined. The present studies examine the effect of protein ingestion on sympathetic function based upon the measurement of [3H]norepinephrine (NE) turnover in heart and interscapular brown adipose tissue (IBAT) as the index of SNS activity. In these experiments, animals were pair-fed mixtures of laboratory chow and refined preparations of casein, sucrose, and lard to permit comparisons among nutrients with total energy intake held constant or with additional energy provided in the form of a single nutrient. After 5 d of eating a 2:1 mixture of chow and either casein or sucrose cardiac, [3H]NE turnover was less (P less than 0.005) in casein-fed rats (6.4%/h and 28.9 ng NE/h) than in animals given sucrose (11.2%/h and 46.5 ng NE/h). Similar results were obtained in IBAT and in experiments using 1:1 mixtures of chow and casein/sucrose. Casein-fed animals also displayed slower rates of NE turnover than lard-fed rats in both heart (7.8%/h vs. 13.2, P less than 0.001) and IBAT (7.0%/h vs. 12.8, P less than 0.01). Addition of casein (50% increase in energy intake) to a fixed chow ration raised NE turnover slightly, but not significantly, in heart (an average increase of 15% in six experiments). Thus, in distinction to SNS activation seen with dietary carbohydrate or fat, the SNS response to dietary protein is minimal in both heart and IBAT, indicating that the effect of increased energy intake on the SNS is dependent upon diet composition.

Adipose Tissue, Brown↗
PubMed2001

Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels.

N-type voltage-dependent Ca(2+) channels (VDCCs), predominantly localized in the nervous system, have been considered to play an essential role in a variety of neuronal functions, including neurotransmitter release at sympathetic nerve terminals. As a direct approach to elucidating the physiological significance of N-type VDCCs, we have generated mice genetically deficient in the alpha(1B) subunit (Ca(v) 2.2). The alpha(1B)-deficient null mice, surprisingly, have a normal life span and are free from apparent behavioral defects. A complete and selective elimination of N-type currents, sensitive to omega-conotoxin GVIA, was observed without significant changes in the activity of other VDCC types in neuronal preparations of mutant mice. The baroreflex response, mediated by the sympathetic nervous system, was markedly reduced after bilateral carotid occlusion. In isolated left atria prepared from N-type-deficient mice, the positive inotropic responses to electrical sympathetic neuronal stimulation were dramatically decreased compared with those of normal mice. In contrast, parasympathetic nervous activity in the mutant mice was nearly identical to that of wild-type mice. Interestingly, the mutant mice showed sustained elevation of heart rate and blood pressure. These results provide direct evidence that N-type VDCCs are indispensable for the function of the sympathetic nervous system in circulatory regulation and indicate that N-type VDCC-deficient mice will be a useful model for studying disorders attributable to sympathetic nerve dysfunction.

Animals↗
PubMed2000

Sympathetic nervous system activity and female sexual arousal.

The results of a series of human and animal studies that were conducted in an effort to better understand autonomic nervous system influences on female sexual arousal are presented. The effects of sympathetic nervous system (SNS) activation on self-report and vaginal photoplethysmographic measures of sexual arousal were examined in 4 studies using intense acute exercise, and in 1 study using ephedrine, to activate the SNS. The effects of SNS inhibition on sexual responses in the female rat were examined in 3 studies using clonidine, an alpha(2)-adrenergic agonist; guanethidine, a postganglionic noradrenergic blocker; and naphazoline, an alpha(2)-adrenoreceptor agonist, to inhibit sympathetic outflow. In humans, the effects of SNS inhibition on subjective and physiologic sexual arousal were also examined using clonidine to suppress SNS activity. Together, the findings from these studies suggest that SNS activation may facilitate, and SNS inhibition inhibit, the early stages of sexual arousal in sexually functional women and in women with low sexual desire.

Animals↗
PubMed1999

The protective effect of the sympathetic nervous system against acoustic trauma.

OBJECTIVE: the cochlea is innervated by the sympathetic nerve fibers. However, the functions of those fibers in the cochlea are still controversial. The present study was designed to determine whether the sympathetic nervous system (SNS) exerts a protective or enhancing effect on acoustic trauma. METHODS: acoustic overstimulation (either of 110, 115, or 130 dB SPL for 10 min) was performed in guinea pigs during electrical stimulation of the ipsilateral cervical SNS, after its surgical elimination or in the non-treated condition. The threshold shift of the compound action potential (CAP) from the pre-exposure value was measured at 1 h and at 1 week after acoustic overstimulation. Two-way analyses of variance (ANOVAs) were completed for the SNS conditions and the frequencies. RESULTS: although no significant difference was found at 1 h after overstimulation among these three groups, the CAP threshold shift at 1 week (110 and 115 dB SPL) was significantly smaller in the SNS stimulation group than in the other two groups. CONCLUSION: a protective effect was observed in the SNS stimulation group 1 week after the exposure to acoustic overstimulation of moderate intensity (from 110 to 115 dB SPL for 10 min).

Acoustic Stimulation↗
PubMed1985

Role of the sympathetic nervous system in functional maturation of Müller's smooth muscle in the rat.

The role of the sympathetic nervous system (SNS) in postnatal functional maturation of Müller's smooth muscle was evaluated in urethane-anesthetized Sprague-Dawley rats. Guanethidine treatment beginning at birth induced complete sympathectomy, as determined by abolition of contractile responses to electrical stimulation of preganglionic axons and tyramine. Through 45 days of age, sympathectomy had little effect on development of contractile responses to stimulation of alpha-1 adrenoceptors by methoxamine. In contrast, sympathectomy prevented the 2-fold increase in contractile response which normally occurs between 45 and 70 days. Similarly, treated preparations were supersensitive to methoxamine (decreased ED50) only after 45 days. Neonatal decentralization of sympathetic neurons also prevented the increase in methoxamine response occurring after 45 days. Treatment of mature rats with guanethidine from 70 to 100 days of age resulted in a 40% reduction in force of contraction. It is concluded that: the SNS is not obligatory for Müller's muscle functional maturation through 45 days; the SNS mediates a 2-fold increase in contractile response between 45 and 70 days; the effect of the SNS is impulse-dependent; and the intact SNS is required to maintain end organ function at mature levels.

Animals↗
PubMed2001

Sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy.

BACKGROUND: It is difficult to quantify the impact of surgical trauma on patients with conventional measurement techniques. We report our preliminary experience with the determination of sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy. METHODS: The electroconductivity of representative dermatomes (24 measuring points) was recorded prior, during, and after performing laparoscopic and needlescopic cholecystectomy on 40 consecutive patients according to the method of Nakatani (Ryodoraku). Fifty-five healthy adults served as a control group. RESULTS: Median age in the two groups was 52.4 and 54.1 years, respectively. Prior to the operation and on the 1st postoperative day, sympathetic nervous activity was equal in both groups. In the needlescopic patients, sympathetic activity was lesser at 30 min after the start of the laparoscopic procedure (p <0.05). CONCLUSIONS: The measurement of electroconductivity is a useful noninvasive technique for the evaluation of sympathetic nervous activity. As far as activation of sympathetic nervous system is concerned, the needlescopic technique was found to be superior.

Adult↗