Basal Plasma Norepinephrine Research Articles

New approach for measurement of sympathetic nervous abnormality in conscious, spontaneously hypertensive rats.

We previously reported a highly sensitive chemiluminescence high-performance liquid chromatographic method to determine catecholamines in plasma. In this study, we employed this method to measure the cardiac function and plasma norepinephrine (NE) concentration in conscious rats. Benidipine, 1,4-dihydropyridine calcium antagonist (4 mg/kg), and beta-blocker (propranolol, 30 mg/kg) were administered orally to conscious spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats, and blood pressure, heart rate and plasma NE levels were measured. Plasma NE concentration was used as an index of sympathetic nervous system activity in conscious rats. The basal plasma NE levels were significantly higher in SHRs than in WKY rats (P<0.05), indicating the activity of the basal sympathetic nervous system in SHRs was elevated. The sensitivity of the baroreflex-mediated sympathetic nervous response was reduced in SHRs as compared to that in WKY rats. The concomitant administration of benidipine and a beta-blocker decreased heart rate without affecting the baroreflex-mediated sympathetic nervous response, indicating that propranolol might suppress mainly the cardiac beta-adrenoceptor. The present study suggested the high activity of the basal sympathetic nervous system and the reduced response of the baroreflex-mediated sympathetic nervous system in SHRs compared to WKY rats in the conscious condition.

Effect of aging on β-adrenergically mediated thermogenesis in men

The age-dependent alterations in beta-adrenergically mediated thermogenesis were investigated in 11 young (mean +/- SE age: 21.9 +/- 0.5 yr) and 9 older (52.9 +/- 2.1 yr) men during intravenous infusion of the nonselective beta-agonist isoprenaline (Iso). The older men had higher basal plasma norepinephrine (327.7 +/- 35.8 vs. 159.0 +/- 18.2 pg/ml, P < 0.001) and epinephrine (75.1 +/- 18.1 vs. 29.1 +/- 5.3 pg/ml, P < 0.05) concentrations than the young. The beta-adrenergically mediated thermogenesis was diminished in the older men, as reflected by the significantly higher plasma Iso concentration needed to increase resting energy expenditure by 15% (236.1 +/- 51.0 vs. 107.6 +/- 11.4 pg/ml, P < 0.05). Additionally, both dose (39.4 +/- 6.6 vs. 19.1 +/- 1.5 ng . kg fat-free mass-1 . min-1, P < 0.01) and plasma concentration (332.2 +/- 59.1 vs. 119.3 +/- 14.0 pg/ml, P < 0.01) of Iso needed to increase resting heart rate by 25 beats/min were higher in older than in younger subjects, suggesting that the age-related decline in beta-adrenergic sensitivity is a generalized defect not related to a specific tissue or response. In conclusion, aging is associated with a diminished beta-adrenergically mediated thermogenesis. This blunted thermogenic response may contribute to a positive energy balance and thus promote increased fat storage and obesity.

The relationship between plasma MHPG and NE: employing regression models in estimating centrally derived MHPG and peripheral NE turnover rate in panic disorder

Studies investigating the role of the noradrenergic system in the pathophysiology of anxiety have focused on measuring plasma 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels. Fewer studies have examined norepinephrine levels. Basal plasma norepinephrine and free MHPG levels were simultaneously measured in 33 normal controls and 20 panic disorder (PD) patients. Norepinephrine levels were similar in patients and controls, but MHPG levels were significantly lower in patients (13.34 ± 3.22 vs 18.37 ± 4.49pmolml −1, p < 0.0001.gif">). Norepinephrine correlated significantly with plasma MHPG levels in controls ( r = 0.538, p < 0.0001) and patients ( r = 0.645, p < 0.002). Patients had a trend toward a lower y-intercept than controls, suggesting a lower contribution by the CNS to MHPG pool plasma levels (9.18 vs 12.51, p < 0.08). Norepinephrine turnover rate was similar in patients and controls. We propose that the dysregulation in the noradrenergic system in PD may be akin to animal studies of acute-on-top-of-chronic stress paradigms, whereby chronic stress results in normal or decreased basal NE turnover and sensitized responses to recurrent stresses.

Improvement of insulin sensitivity by short-term exercise training in hypertensive African American women.

African American women have a high prevalence of insulin resistance, non-insulin-dependent diabetes mellitus, obesity, and hypertension that may be linked to low levels of physical activity. We sought to determine whether 7 days of aerobic exercise improved glucose and insulin metabolism in 12 obese (body fat >35%), hypertensive (systolic blood pressure > or =140 and/or diastolic blood pressure > or =90 mmHg) African American women (mean age 51+/-8 years). Insulin-assisted frequently-sampled intravenous glucose tolerance tests were performed at baseline and 14 to 18 hours after the 7th exercise session. There was no significant change in maximal oxygen consumption, body composition, or body weight after the 7 days of aerobic exercise. The insulin sensitivity index increased (2.68+/-0.45 x 10[-5] to 4.23+/-0.10 x 10[-5] [min(-1)/pmol/L], P=.02). Fasting (73+/-9 to 50+/-9 pmol/L, P=.02) and glucose-stimulated (332+/-58 to 261+/-45 pmol/L, P=.05) plasma insulin levels decreased. Additional measures related to the insulin resistance syndrome also changed with the 7 days of exercise: basal plasma norepinephrine concentrations were reduced (2.46+/-0.27 to 1.81+/-0.27 nmol/L, P=.02) and sodium excretion rate increased from 100+/-13 to 137+/-7 mmol/d (P=.03); however, there was no change in potassium excretion or 24-hour ambulatory blood pressure. We conclude that a short-term aerobic exercise program improves insulin sensitivity in African American hypertensive women independent of changes in fitness levels, body composition, or body weight. The present study indicates that short-term exercise can improve insulin resistance in hypertensive, obese, sedentary African American women and confirms previous reports that a portion of the exercise-induced improvements in glucose and insulin metabolism may be the result of recent exercise.

Alpha-2 adrenergic activity in perimenopausal women.

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F = 0.7, p = NS; F = 0.2, p = NS and F = 0.1, p = NS respectively) between PeriMW both before and after therapy and PreMW. Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F = 0.8, p = NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F = 12; p < 0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F = 1.2, p = NS; F = 0.5, p = NS and F = 1.3, P = NS respectively). HR decreased significantly after clonidine in PreMW (F = 5.4, p < 0.03) but not in PeriMW before (F = 1.0, p = NS) and during estrogen therapy (F = 0.5, p = NS). Clonidine did not affect plasma E in the three groups studied (F = 2.8, p = NS; F = 2.2, P = NS and F = 0.1, p = NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

Plasma noradrenaline and ageing: effects of smoking habits.

We tested the hypothesis that long-term smoking is responsible for increased plasma noradrenaline (NA) in elderly healthy subjects. Thirty-nine subjects were studied both at rest and during exercise: 10 young non-smokers (median age 24 years, range 21-33), 10 young smokers (30.5 years, 27-36), 10 elderly non-smokers (64 years, 52-75) and nine elderly smokers (62 years, 56-68). The young and elderly subjects had smoked for an average of 15 years and 46.8 years respectively. Plasma NA was significantly elevated in elderly long-term smokers compared with elderly non-smokers, young non-smokers and young smokers in both supine and sitting positions (supine: 1.06 +/- 0.24 vs. 0.71 +/- 0.22, 0.53 +/- 0.12, and 0.70 +/- 0.29 nmol L-1 respectively; sitting: 3.01 +/- 0.83 vs. 2.07 +/- 0.77, 1.89 +/- 0.52 and 2.25 +/- 0.47 nmol L-1 respectively). Plasma adrenaline did not differ among the groups. At submaximal exercise (60 W), plasma NA was significantly elevated in the elderly smokers compared with the other groups, owing to the elevated basal values. Increments in plasma NA at 60, 100 and 140 W were correlated with the relative exertion and not influenced by smoking. Plasma NA increased more in young subjects than in the elderly during maximal work load (21.7 +/- 8.0 vs. 13.4 +/- 5.4 nmol L-1) and correlated with the peak O2 uptake. Total blood volume was not different among the four groups and correlated inversely with basal plasma NA. It is concluded that long-term smoking may contribute to increased basal plasma NA concentrations and probably also increased sympathetic nerve activity in elderly healthy subjects, whereas smoking has little if any effect on plasma NA responses induced by exercise. Interindividual variability in basal plasma NA concentrations may in part be explained by differences in blood volume.

Nocturnal blood pressure elevation is related to adrenomedullary hyperactivity, but not to hyperinsulinemia, in nonobese normoalbuminuric type 1 diabetes.

We tested the hypothesis that insulin is an independent risk factor for elevated blood pressure. As our model we selected type 1 diabetes with peripheral circulatory hyperinsulinemia induced by sc insulin treatment. In 15 nonobese normoalbuminuric patients with type 1 diabetes (23.7 +/- 0.8 yr old) and in 15 healthy controls matched for age, sex, and body weight, ambulatory blood pressure was recorded over 24 h. The areas under the curve of free insulin (605 +/- 135 vs. 275 +/- 35 pmol/L.h; P = 0.03) and basal plasma epinephrine concentrations were higher (170 +/- 10 vs. 130 +/- 10 pmol/L; P = 0.02), and the basal aldosterone level was lower (220 +/- 40 vs. 410 +/- 50 pmol/L; P = 0.009) in the patients. The nocturnal decline in systolic blood pressure was less pronounced (13 +/- 1 vs. 19 +/- 2 mm Hg; P = 0.007) in the patients. Multivariate adjustment (r2 = 0.75; P = 0.0002) showed an effect of basal plasma epinephrine and norepinephrine levels and body mass index on the mean nocturnal systolic blood pressure, but showed no effect of age, sex, hemoglobin A1c, aldosterone, or, in particular, insulin. We found a blunted nocturnal fall in blood pressure in nonobese, normoalbuminuric type 1 diabetic patients. These patients showed increased adrenomedullary activity, and this predominantly contributed to the blood pressure alterations. We also found hyperinsulinemia in these patients, but, after controlling for covariates, blood pressure was independent of the insulin level.

Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats

In this study, we tested the hypothesis that, in the male Fischer 344 x Brown Norway (F344xBN) rat, aging would be associated with an increase in sympathetic nervous system activity and a decrease in skeletal muscle beta-adrenergic-receptor (beta-AR) density and function. Radioligand-binding studies using [125I] iodocyanopindolol were done to evaluate beta-AR density (Bmax) and antagonist-binding affinity in gastrocnemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rats. beta-AR function was measured as adenylyl cyclase (AC) activity stimulated by the beta-AR agonist isoproterenol (Iso, 10(-4) M). Basal arterial plasma norepinephrine (pNE) concentrations were higher in the 28-than in the 6- and 18-mo-old rats. Bmax was greatest and Iso-stimulated AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in Bmax and Iso-stimulated AC activity in cardiac muscle. In conclusion, there was an age-associated increase in pNE concentrations in male F344xBN rats, suggesting an increase in sympathetic nervous system activity. In addition, there was an age-associated increase in skeletal muscle beta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activity remained unchanged with age.

Effects of exposure to stressors of varying predictability on adrenal function in rats.

For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66, or 100% of the time. Basal hormone levels and responses to a light-shock pair were measured daily. Greater predictability was associated with higher basal plasma corticosterone and norepinephrine levels indicative of chronic stress. Habituation of the corticosterone response was also less in the groups with greater predictability. However, predictability did not affect plasma prolactin or epinephrine responses. Because the endocrine systems responded differently, it is unlikely that the changes were due to a unitary process. Greater predictability appeared to be more stressful in this paradigm. Both associative and nonassociative factors have major roles in determining the hormonal responses to repeated presentation of stressors.

β-Adrenergically mediated thermogenic and heart rate responses: Effect of obesity and weight loss

β-Adrenergically mediated thermogenic and heart rate (HR) responses, as assessed by stepwise intravenous infusion of the β-agonist isoprenaline (ISO), were evaluated by partial regression analysis in a group of men with a wide range of body fat (n = 30) and in a subgroup of 16 obese men after weight loss. β-Adrenergically mediated thermogenesis (open-circuit ventilated-hood system) was blunted in obese subjects, as reflected by a significant positive correlation between percent body fat (hydrostatic weighing) and the plasma ISO concentration needed to increase resting energy expenditure (EE) by 15% ( P < .001). The magnitude of the β-adrenergically mediated HR response was (negatively) associated with the basal plasma norepinephrine (NE) concentration ( P < .001). Weight reduction resulted in a significant increase in thermogenic and HR responses in obese subjects. Furthermore, the increase in thermogenic response as a result of weight loss was negatively related to the magnitude of thermogenic response ( P < .01) and positively related to the initial percent body fat ( P < .05). The increase in HR response as a result of weight loss was positively related to the decrease in basal NE ( P < .01) and the change in percent body fat ( P < .05). In conclusion, the degree of adiposity was shown to be negatively related to the magnitude of β-adrenergically mediated thermogenesis, whereas the HR response was merely related to basal NE. Since weight loss resulted in a significant increase in the thermogenic response, the blunted β-adrenergically mediated thermogenesis does not seem to be a primary factor contributing to the development of obesity.

Stepped care medical treatment for cirrhotic ascites: Analysis of factors influencing the response to treatment

Thirty-two patients with liver cirrhosis and ascites were treated by stepped care diuretic treatment as follows: step 1, placed on a 35 mEq sodium diet; step 2, given 400 mg/day of potassium canrenoate in addition to step 1 treatment; step 3, given 40-80 mg/day of furosemide in addition to step 2 treatment. Eleven out of 32 patients (34.4%, group 1) and 12 of 21 patients (57.1%, group 2) lost their ascites at step 1 and step 2, respectively. The remaining nine patients (group 3) required step 3 treatment. Basal urinary sodium excretion and creatinine clearance were significantly lower and beta 2-microglobulin was significantly higher in group 3 than those in groups 1 and 2. Elevation of basal plasma renin activity and norepinephrine was evident only in group 3. In group 1, urinary sodium excretion decreased after the treatment. In group 2, plasma alpha-atrial natriuretic polypeptide was lowered and plasma renin activity and norepinephrine were elevated after the treatment. These results suggest that basal renal function and plasma renin activity and norepinephrine levels are useful indices to predict the effect of ascites treatment and that responders to sodium restriction or potassium canrenoate may be in the state of vascular overflow, while non-responders to potassium canrenoate may be in the state of vascular underfilling. In summary, this stepped care treatment is safe without any side effects, although the diuretics themselves may lead to relative vascular underfilling.

Effects of exposure to stressors of varying predictability on adrenal function in rats.

For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66, or 100% of the time. Basal hormone levels and responses to a light-shock pair were measured daily. Greater predictability was associated with higher basal plasma corticosterone and norepinephrine levels indicative of chronic stress. Habituation of the corticosterone response was also less in the groups with greater predictability. However, predictability did not affect plasma prolactin or epinephrine responses. Because the endocrine systems responded differently, it is unlikely that the changes were due to a unitary process. Greater predictability appeared to be more stressful in this paradigm. Both associative and nonassociative factors have major roles in determining the hormonal responses to repeated presentation of stressors.

Sympathetic overactivity and 24-hour blood pressure pattern in hypertensives with chronic renal failure.

In order to assess the activity of the sympathetic system and to evaluate the 24-h blood pressure pattern in hypertensives with chronic renal failure (CRF), 12 CRF patients and 16 essential hypertensives (EHs) were studied. In all subjects, plasma samples for catecholamines and renin activity were obtained both in the basal condition and after standing, and 24-h blood pressure monitoring (ABPM) was performed. The 24-h mean blood pressure results were quite similar between CRFs and EHs. In 50% of the CRFs, ABPM showed a nighttime decrease in diastolic BP (DBP) greater than 10%, while in the remaining 50% the ABPM indicated a nondipper blood pressure pattern. Of the 16 EHs, 4 had a nighttime decrease in DBP < 10%, that is, nondippers. The study of circulating catecholamines showed no significant differences in plasma epinephrine between CRFs and EHs, while plasma norepinephrine (NE) was significantly higher in hypertensives with CRF than in EHs, both at rest and after standing (p < 0.05 and 0.02, respectively). Among dipper hypertensives, subjects with CRF showed greater values of basal plasma NE than EHs (535 +/- 67 vs. 412 +/- 24.5 pg/mL, p < 0.05); the comparison between dipper and nondipper CRFs showed no differences in circulating NE levels (535 vs. 516 pg/mL). The present study shows that CRFs are characterized by higher values of plasma NE than EHs, and that there are no differences in sympathetic activity between dipper and nondipper hypertensives with CRF.

Circulating dihydroxyphenylglycol and norepinephrine concentrations during sympathetic nervous system activation in patients with pheochromocytoma.

Although increased plasma norepinephrine (NE) concentrations mediate vasoconstriction during episodic hypertension and hypertensive crises in patients with pheochromocytoma (Pheo), the precise origin of this circulating NE (tumor or sympathetic nerves) is not known. Dihydroxyphenylglycol (DHPG), a deaminated metabolite of NE, is formed principally in sympathetic nerve endings. Under basal conditions, plasma NE and DHPG concentrations correlate closely, and during sympathetic nervous system activation, both plasma NE and DHPG concentrations increase. This observation suggests that plasma DHPG concentrations may reflect the source of circulating NE (tumor or sympathetic nerves) during hypertensive episodes in patients with Pheo. Plasma NE and DHPG concentrations were measured simultaneously, and the NE/DHPG ratio was calculated in seven patients with Pheo during 20 min of sympathetic nervous system activation (treadmill exercise) before and after surgical resection of the tumor. Age- and sex-matched normal subjects were also studied. Exercise resulted in a significant increase in plasma NE and DHPG concentrations in patients with Pheo and in normal subjects (Pheo: basal NE, 1827 +/- 639; peak NE, 3016 +/- 769 pg/mL (P = 0.02); normal subjects: basal NE, 266 +/- 27; peak NE, 1166 +/- 197 pg/mL (P = 0.01); Pheo: basal DHPG, 1521 +/- 280; peak DHPG, 2313 +/- 252 pg/mL (P = 0.007); normal subjects: basal DHPG, 870 +/- 50; peak DHPG, 1630 +/- 180 pg/mL (P = 0.01)]. The NE/DHPG ratio increased with exercise in normal subjects (basal, 0.30 +/- 0.02; peak, 0.83 +/- 12; P = 0.005), but did not change in patients with Pheo (basal, 1.22 +/- 0.32; peak, 1.54 +/- 0.27). Exercise also increased plasma NE and DHPG concentrations and the NE/DHPG ratio in five patients studied after surgical resection of the tumor. Systolic blood pressure and heart rate increased significantly during exercise in all three study groups. The increase in plasma NE and HDPG concentrations during exercise-induced sympathetic nervous system stimulation in patients with Pheo is similar to that in normal subjects and may indicate that the sympathetic nervous system plays an important role in the pathogenesis of hypertension and hypertensive crises in patients with Pheo.

Endurance exercise training is associated with elevated basal sympathetic nerve activity in healthy older humans

We tested the hypothesis that endurance training is associated with altered basal levels of muscle sympathetic nerve activity (MSNA) and responses to acute stress in healthy older adults. MSNA (peroneal microneurography) and plasma norepinephrine (NE) concentrations were measured during supine rest, a cold pressor test, and isometric handgrip (40% maximal voluntary force to exhaustion) in 16 older masters endurance athletes [10 men, 6 women; 66 +/- 1 (SE) yr] and 15 healthy normotensive untrained control subjects (9 men, 6 women; 65 +/- 1 yr). The athletes had higher levels of estimated daily energy expenditure and maximal oxygen uptake and lower levels of resting heart rate and body fat than the control subjects (all P < 0.05). MSNA during supine rest was elevated in the athletes whether expressed as burst frequency (43 +/- 2 vs. 32 +/- 3 bursts/min, respectively; P < 0.05) or burst incidence (75 +/- 4 vs. 52 +/- 5 bursts/100 heartbeats, respectively; P < 0.01). These whole group differences were due primarily to markedly higher levels of MSNA in the athletic vs. untrained women (48 +/- 4 vs. 25 +/- 3 bursts/min, 82 +/- 3 vs. 38 +/- 3 bursts/100 heartbeats, respectively, P < 0.001). In contrast, basal plasma NE concentrations were not significantly different in the athletes vs. control subjects. The MSNA and plasma NE responses to acute stress tended to be greater in the athletes. These findings indicate that vigorous regular aerobic exercise is associated with an elevated level of MSNA at rest and a tendency for an enhanced response to acute stress in healthy normotensive older humans.

Heterogeneity of prejunctional neuropeptide Y receptors inhibiting noradrenaline overflow in the portal vein of freely moving rats

The effects of intraportal infusions of different doses of neuropeptide Y, its selective neuropeptide Y Y 1 receptor analogue, [Leu 31,Pro 34]neuropeptide Y, and the Y 2-selective C-terminal fragment, neuropeptide Y-(18–36), on basal and electrically evoked noradrenaline overflow in the portal vein as well as on mean arterial pressure and heart rate were investigated in permanently instrumented freely moving rats. Neuropeptide Y dose dependently (2–2000 ng/kg/min) attenuated the electrically evoked noradrenaline overflow and almost complete blockade was reached at the highest dose used. [Leu 31,Pro 34]Neuropeptide Y also dose dependently (20–20 000 ng/kg/min) attenuated the evoked overflow, reaching a maximum of 55% inhibition at the highest dose (20 000 ng/kg/min). Neuropeptide Y-(18–36) attenuated the evoked release only at 20 000 ng/kg/min (by 46%). Only at the highest dose did neuropeptide Y (2000 ng/kg/min) and [Leu 31,Pro 34]neuropeptide Y (20 000 ng/kg/min) significantly enhance mean arterial pressure and decrease heart rate and basal plasma noradrenaline levels, the latter two effects being due to the baroreceptor reflex. Neuropeptide Y-(18–36) did not influence these parameters at all doses used. The results indicate the presence of prejunctional neuropeptide Y Y 1 receptors, and possibly the coexistence of Y 1 and Y 2 receptors, in the portal vein of freely moving rats, which in conjunction are able to inhibit markedly electrically evoked noradrenaline overflow. Postjunctional neuropeptide Y receptors mediating an increase in blood pressure in the freely moving rat are solely of the Y 1 subtype.

Effect of Magnesium Sulfate Infusion on Circulating Levels of Noradrenaline and Neuropeptide-Y-Like Immunoreactivity in Patients with Primary Raynaud's Phenomenon

The effect of a short-term magnesium sulfate (MgSO4) infusion on venous plasma concentration of noradrenaline (NA) and neuropeptide-Y-like immunoreactivity (NPY-LI) was investigated in 12 women with primary Raynaud's phenomenon (PRP) and in 12 healthy matched controls. The Raynaud's patients did not demonstrate any significant changes in mean basal plasma NA concentration (0.29 +/- 0.15 vs 0.37 +/- 0.09 ng/mL, ns) after MgSO4 infusion. However, in the controls there was more than twice the amount of circulating noradrenaline (cNA) (0.21 +/- 0.14 vs 0.54 +/- 0.22 ng/mL, P < 0.001) after MgSO4 infusion, compared with the preinfusion value. Measurements during the cold pressor test prior to the MgSO4 infusion showed a significant increase of cNA in both the PRP group and the control group (from 0.29 +/- 0.15 to 0.33 +/- 0.16 ng/mL, P < 0.05, and from 0.21 +/- 0.14 to 0.29 +/- 0.16 ng/mL, P < 0.005, respectively). After MgSO4 infusion the levels of cNA during the cold pressor test increased significantly only in the PRP group (from 0.37 +/- 0.09 to 0.41 +/- 0.11 ng/mL, P < 0.05). Circulating NPY-LI concentrations increased significantly during MgSO4 infusion in the Raynaud's patients as well as in the controls from 105 +/- 21 to 127 +/- 23 pmol/L, P < 0.05, and from 107 +/- 17 to 132 +/- 27 pmol/L, P < 0.01, respectively. There were no detectable changes during the cold pressor tests in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Overfeeding-induced obesity in rats: Insulin sensitivity and autonomic regulation of metabolism

The metabolic consequences of the development of obesity and the underlying mechanisms were investigated. For this purpose, male rats were overfed for 5 weeks through long-term gastric catheters. Permanent cardiac cannulas implanted before the overfeeding period allowed frequent blood sampling and infusions without disturbing the rats. Hyperalimented rats became grossly obese, displayed elevated basal plasma norepinephrine (NE) concentrations, and developed hyperinsulinemia and insulin insensitivity, but remained normoglycemic and preserved normal intravenous (IV) glucose tolerance. During physical exercise (ie, 15 minutes of swimming), obese rats displayed exaggerated increases in blood glucose concentrations, whereas plasma free fatty acid (FFA) responses were blunted. These alterations were probably due to decreased NE release by the sympathetic nervous system during exercise and to altered tissue responsivity to adrenergic stimulation. The latter was demonstrated by infusions of catecholamines in the resting state. Responses to mild stress were increased in obese animals, as indicated by increased responses of plasma epinephrine (E) and corticosterone during handling and first contact with water. The results of the present study indicate that overfeeding induces changes in the sympathetic control of metabolism and insulin secretion. Whereas elevated NE levels in the basal state probably reflect increased energy expenditure, the pattern of nutrient mobilization during exercise is directed toward sparing of fats.

A nonsecreting pheochromocytoma presenting as an incidental adrenal mass. Report on a case

A 25 year old women presented an incidental adrenal mass which was diagnosed to be a pheochromocytoma before surgery by means of a positive 131-I-MIBG scintigraphy. Urinary vanilmandelic acid resulted repeatedly normal as well as basal plasma norepinephrine (NE), epinephrine (E) and dopamine (DA). Urinary homovannilic acid resulted in the normal range. Stimulation tests with iv glucagone, tyramine and metoclopramide evoked normal NE and E responses while a slight increase in plasma DA was observed after metoclopramide. Oral clonidine suppressed plasma catecholamines (CA) normally. Histologic and immunohistochemical studies confirmed that the tumor was a pheochromocytoma showing positivity for tyrosine hydroxylase but not for dopamine-beta-hydroxylase activity. This case is the first report on a completely asymptomatic pheochromocytoma presenting as an incidental adrenal mass which was investigated with repeated biochemical tests before surgery and demonstrates that, among the extremely variable functional attitudes of pheochromocytomas, a defect in CA synthesis and secretion is also to be included.

Role of Plasma Catecholamines, Autonomic, and Left Ventricular Function in Normotensive and Hypotension Prone Dialysis Patients

The current study looked at plasma catecholamines, clinical autonomic function tests, and hemodynamic parameters in 10 ESRD patients (five men and five woman, aged 56.4 +/- 3.6) with dialysis hypotension and 10 patients (five men and five women, aged 58.6 +/- 4.2) without dialysis hypotension. Catecholamines were measured using high performance liquid chromatography--electrochemical detection (HPLC-ECD). Dialysis led to a significant decrease in mean arterial pressure (MAP) in the hypotensive group as compared with the normotensive group. Significantly higher basal (predialysis) plasma norepinephrine (NE) and dopamine levels (DA) were found in the hypotensive uremic group as compared with the normotensive group. Levels of plasma epinephrine (EP) were not significantly different between the normotensive and hypotensive groups. In response to postural stimulation, blood pressure fell in both groups, but the fall in the hypotensive group was significantly greater. Percentage increments of plasma catecholamines in response to postural stimulation in both groups were similar, however. Among the measured hemodynamic parameters, including total peripheral vascular resistance and left ventricular function (cardiac index and fractional shortening), only the cardiac index showed significantly lower values in the hypotensive group after dialysis, as compared with the normotensive group. Results of four tests of autonomic function indicated that although both groups responded similarly to hand-grip and cold-pressor tests, impaired responses to orthostasis and Valsalva maneuver after dialysis were observed in the hypotensive group. The MAP changes in dialysis in the hypotension prone group correlated inversely with predialysis plasma NE, but not with EP and DA.(ABSTRACT TRUNCATED AT 250 WORDS)