Effect of beta blockade on plasma catecholamine levels during psychological and exercise stress

The effect of a single oral dose of 50 mg of metoprolol on plasma catecholamine levels was examined in 11 healthy young men. Subjects were studied during baseline at rest, postural challenge, psychological Stressors and graded maximal exercise testing. Metoprolol induced significant increases in plasma norepinephrine (NE) levels across most experimental conditions. Metoprolol did not have a consistent effect on plasma epinephrine levels. Because of wide interindividual variation in drug levels, the NE levels in subjects with high drug levels were compared with the NE levels in subjects who had negligible drug levels. NE levels were higher in subjects with higher drug levels.     

Response of plasma norepinephrine and epinephrine to dynamic exercise in patients with congestive heart failure

The activity of the sympathetic nervous system is increased at rest in patients with congestive heart failure. To determine whether this augmentation is carried over during dynamic upright exercise, 14 patients with congestive heart failure were stressed maximally during upright bicycle ergometry. Plasma norepinephrine and epinephrine levels were measured in the basal upright (sitting) posture before and during maximal exercise. The results were compared with those in six healthy control subjects before and during maximal exercise. Plasma norepinephrine increased during exercise from a mean (± standard error of the mean) of 650 ± 95 to 1,721 ± pg/ml in the group with heart failure. This increase was significantly less (p < 0.001) than that in the control group (from 318 ± 36 to 3,230 ± 418 pg/ml). However, for equivalent levels of total body oxygen consumption (V?O₂), the group with heart failure had higher levels of plasma norepinephrine than the control group. Plasma epinephrine was similar in the two groups in the basal upright position (92 ±18 and 92 ± 26 pg/ml), but it increased more during exercise in the normal subjects (743 ± 210 pg/ml) than in the group with heart failure (167 ± 67 pg/ml) (p < 0.001). The percent increase in norepinephrine correlated with the percent change in V?O₂ in the group with heart failure (r = 0.62, p < 0.02), but the percent change in epinephrine did not.There is, therefore, a disturbance in the sympathetic nervous system during exercise in patients with congestive heart failure. Although norepinephrine increases in such patients to a greater extent than in normal subjects at lower levels of exercise, the extremely high levels of norepinephrine and epinephrine generated by normal subjects during maximal upright exercise do not occur in patients with heart failure.     

Comparative effects of epinephrine and norepinephrine on plasma glucose and hematocrit levels in the american bullfrog (Rana catesbeiana).

Adrenal chromaffin tissue of the American bullfrog (Rana catesbeiana) treated by the formaldehyde-induced fluorescence method demonstrated approximately equal numbers of norepinephrine- and epinephrine-containing cells. The effects of a single intra-arterial injection of epinephrine or norepinephrine on plasma glucose and hematocrit levels were compared. Blood was collected from the cannulated sciatic artery. Plasma glucose was estimated by the glucose oxidase method. Plasma glucose levels of starved, untreated bullfrogs were elevated following surgery for the insertion of the cannula, but declined to relatively stable levels from the third (7.0 ± 0.4 mg/100 ml) through the fifth (6.5 ± 0.5 mg/100 ml) postoperative day. Similarly, the postsurgical hematocrit values declined to relatively stable values from the third (13.1 ± 0.5%) through the fifth (11.9 ± 0.5%) postoperative day. Hormones were injected on the fourth or fifth postoperative day. Plasma glucose and hematocrit levels increased within 15 min at all epinephrine doses tested (3, 10, 30, 100, and 300 μg/kg). The magnitude and duration of the responses were related to the dose of epinephrine administered. In contrast, norepinephrine at a dose of 3 μg/kg was ineffective, while at the presumed pharmacologic doses of 300 and 500 μg/kg, norepinephrine resulted in increases in plasma glucose and hematocrit levels that were of lower magnitude and shorter duration than those obtained with 300 μg/kg of epinephrine. Although the physiologic role(s) of norepinephrine in the bullfrog remains unknown, the rapid, dose-dependent, and parallel elevations of plasma glucose and hematocrit levels that followed the injection of epinephrine suggest that this hormone is important in the adaptation of the bullfrog to stressful changes in the environment.     

Effects of fasting on blood plasma levels, metabolism and metabolic effects of epinephrine and norepinephrine in steers

Experiments were designed to study effects of 3 days of fasting on blood plasma levels, metabolic clearance rates (MCR) and effects of norepinephrine (NE) and epinephrine (E) on levels of glucose, nonesterified fatty acids (NEFA) and immunoreactive insulin (IRI) in 12 steers. During fasting, levels of E, NE and protein did not change, whereas IRI, T3 and glucose decreased and NEFA, acetoacetate and beta-hydroxybutyrate increased. Before and at the end of fasting, NE or E were iv infused for 120 min. NE and E were elevated after 15 min and to the end of the infusion. The increase in E, but not in NE, was significantly greater after 3 days of fasting than before fasting (P less than 0.05). MCR for E was lower after fasting (299 +/- 17 vs 204 +/- 10 ml.kg-0.75.min-1; P less than 0.001), whereas MCR for NE was not significantly different (455 +/- 37 vs 400 +/- 27 ml.kg-0.75.min-1). MCR was higher for NE than for E, both before and after fasting (P less than 0.05). After the infusion, E and NE decreased within minutes to pre-infusion concentrations. During E infusions, NEFA increased significantly more, whereas glucose increased less in fasted than in fed animals. During NE infusions, NEFA increased in fasted, but not in fed animals, and glucose increased less at the end than before fasting. IRI decreased during E infusions only in fed animals, and transiently increased after the infusion, except after NE infusion in fasted steers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human plasma ghrelin levels increase during a one-year exercise program

Weight loss resulting from decreased caloric intake raises levels of the orexigenic hormone, ghrelin. Because ingested nutrients suppress ghrelin, increased ghrelin levels in hypophagic weight loss may result from decreased inhibitory input by ingested food, rather than from lost weight. We assessed whether ghrelin levels increase in response to exercise-induced weight loss without decreased caloric intake. We randomized 173 sedentary, overweight, postmenopausal women to an aerobic exercise intervention or stretching control group. At baseline, 3 months, and 12 months, we measured body weight and composition, food intake, cardiopulmonary fitness (maximal oxygen consumption), leptin, insulin, and ghrelin. Complete data were available for 168 women (97%) at 12 months. Exercisers lost 1.4 +/- 0.4 kg (P < 0.05 compared with baseline; P = 0.01 compared with stretchers) and manifested a significant, progressive increase in ghrelin levels, whereas neither measure changed among stretchers. Ghrelin increased 18% in exercisers who lost more than 3 kg (P < 0.001). There was no change in caloric intake in either group and no effect on ghrelin of exercise per se independent of its impact on body weight. In summary, ghrelin levels increase with weight loss achieved without reduced food intake, consistent with a role for ghrelin in the adaptive response constraining weight loss and, thus, in long-term body weight regulation.     

Effect of intrahypothalamic injection of neostigmine on the secretion of epinephrine and norepinephrine and on plasma glucose level.

We previously reported that the injection of neostigmine, an inhibitor of acetylcholinesterase, into the third cerebral ventricle of fasted rats produced hyperglycemia associated with the secretion of epinephrine and norepinephrine. However, the central nervous system site of action of neostigmine by which the plasma catecholamine and glucose concentrations were increased is not known. In this study we injected neostigmine into the ventromedial hypothalamus, lateral hypothalamus, paraventricular hypothalamus, median site of the lateral-preoptic area, lateral site of the lateral-preoptic area, anterior site of the anterior hypothalamic area, mammillary body (posterior mamillary nucleus), and cortex of anesthetized fasted rats and measured the plasma levels of glucose, epinephrine, and norepinephrine. It was found that the ventromedial hypothalamus, lateral hypothalamus, paraventricular hypothalamus, and median site of the lateral-preoptic area were involved in increasing the plasma levels of glucose and epinephrine. From this evidence we conclude that neostigmine acts on selected regions known to be involved in glucoregulation in the hypothalamus to increase the plasma levels of epinephrine and glucose.     

Influence of aging and tyrosine hydroxylase inhibition on tissue levels of norepinephrine during stress

The effect of aging was evaluated on norepinephrine content of the heart (ventricles) and spleen of 3- and 24-month-old F344 and Sprague-Dawley rats utilizing a sensitive radioenzymatic assay. To assess sympathetic nervous system activity, the decline in organ norepinephrine content was compared in young and old F344 rats 6 hours after blockade of norepinephrine synthesis with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. Three conditions were studied: (a) normal, (b) brief starvation (54 hours), and (c) cold exposure (6 hours, 4 degrees C). There was no significant age-related difference in steady state organ norepinephrine concentration. Based on the response to alpha-methyl-p-tyrosine, aging did not affect the rate of heart and spleen norepinephrine synthesis and, therefore, sympathetic nervous system impulse activity during normal or cold stress conditions. Starvation, however, did not suppress sympathetic nervous system activity to the heart in old animals, as it did in the young rats.     

Plasma norepinephrine, epinephrine, and dopamine levels in end-stage renal disease. Effect of hemodialysis

The effect of hemodialysis on plasma norepinephrine (NE), epinephrine, and dopamine levels was studied in 11 patients undergoing maintenance hemodialysis. The results showed that the baseline plasma concentrations of NE and dopamine were significantly elevated in patients with end-stage renal disease undergoing maintenance hemodialysis. Intradialysis weight loss and fall in the serum glucose concentration during dialysis correlated with changes in plasma epinephrine and NE concentrations. Single-pass dialysis resulted in a marked reduction in the plasma NE concentration, indicating significant removal by dialysis. These observations should be taken into consideration when interpreting plasma catecholamine data obtained in the course of investigation of hypertensive patients with end-stage renal disease.     

Plasma normetanephrine and metanephrine levels and their relationship to norepinephrine and epinephrine

To study the relation of normetanephrine (NM) and metanephrine (M) to norepinephrine (NE) and epinephrine (E), plasma free NM (f-NM), free M (f-M), total NM (t-NM) and total M (t-M) were measured in normal subjects and patients with pheochromocytoma (PHEO), neuroblastoma, Cushing's syndrome, primary aldosteronism and chronic renal failure (CRF) by radioimmunoassay. Plasma f-NE and E were measured by radioenzymatic assay. Both f- and t-NM were high in PHEO, neuroblastoma and CRF. f- and t-M were also high in some patients with PHEO and CRF. Positive correlation was observed not only in f-NE with f-NM and t-NM, but also in f-E with f-M and t-M except for CRF. Although upright posture induced an elevation in f-NE and f-NM, t-NM was unchanged in normal subjects. In patients with PHEO, metoclopramide induced a prompt elevation in f-NE and E but no-change in t-NM and M levels. f-NE, f-E, f-NM, t-NM, f-M and t-M decreased rapidly after the resection of PHEO and reached the normal level on the third day after the surgery. In CRF patients, f-NM, t-NM, f-M and t-M decreased after hemodialysis despite an increase of f-NE. From these results, it was suggested that plasma NM and M levels reflected plasma NE and E to a certain extent in normal subjects and patients with normal renal function, and that the impaired renal function provoked an elevation of plasma NM and M due to the accumulation of them.     

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of endurance exercise training on plasma pancreatic polypeptide concentration during exercise

The effect of exercise on human pancreatic polypeptide (hPP) levels was evaluated in five subjects preceding and following a conditioning program. During 90 min of exercise, the plasma concentration of hPP rose to a peak value five times higher than the resting level. After 2 mo of endurance exercise training, exercising at the same absolute work load resulted in only a twofold increase in hPP levels. Even at a higher work load, plasma hPP levels were significantly lower than the values observed prior to conditioning. These results show that plasma hPP concentrations rise during exercise and the magnitude of this response is significantly lower after 2 mo of endurance exercise training.     

Dynamic responses of active and inactive renin and plasma norepinephrine during exercise in normal man

Active and inactive plasma renin, plasma angiotensin II, and plasma norepinephrine were measured during graded exercise. Five health subjects exercised on bicycle ergometer at three different loads (50, 70, and 100% of maximal oxygen uptake). Active plasma renin and plasma angiotensin II were elevated significantly during graded exercise, but plasma inactive renin decreased during the heaviest exercise; the mean ratio of active renin to total renin increased from 57 to 92% after the heaviest load. Plasma norepinephrine was also elevated during graded exercise. There is a positive correlation between plasma norepinephrine and active plasma renin during graded exercise (r = 0.916, p less than 0.01). Similar norepinephrine and active renin responses to graded exercise suggest that the mechanism(s) for activation of inactive renin and the release of active renin from the kidney may be partially related to sympathetic nervous system activity.     

Effects of sodium supplementation during energy restriction on plasma norepinephrine levels in obese women

We tested whether sodium restriction would counteract the decrease in sympathetic nervous system activity usually associated with marked energy restriction. The effects of two levels of energy restriction, with different sodium intakes, on plasma norepinephrine (NE) levels while supine and in response to standing were studied. Twenty-two healthy normotensive obese female subjects (body mass index, 34 +/- 1 kg/m2; weight, 90 +/- 2 kg) followed one of three 3-week protocols: 1) total fasting with 80 mmol/day NaCl, 2) a very low energy diet (VLED) containing 1.7 MJ, 93 g protein, and 90 mmol Na/day, with an additional 60 mmol/day NaCl supplement, or 3) total fasting without NaCl (0 Na fast). At the end of the baseline isocaloric diet and of total fasts or VLED, pulse, blood pressure, and plasma NE were measured after 4 h of recumbency and 5 and 10 min after assuming the upright posture. These measurements were repeated after 1 L physiological saline was infused into the 0 Na fast subjects. Cumulative negative sodium balance was observed only in the 0 Na fasting subjects. Supine blood pressure decreased from baseline with fasting, but not with the VLED. The decreases in systolic pressure and increases in heart rate on standing observed with all diets were greatest with the 0 Na fast. Supine plasma NE (vs. baseline value) declined (P less than 0.05) with the VLED, remained unchanged with the Na supplemented fast, but increased with the 0 Na fast (P less than 0.05). The upright plasma NE values were highest in the 0 Na fast subjects, but lower after the saline infusion as well as in the subjects on the VLED. Thus, the decrease in NE due to energy restriction with normal sodium intake was counteracted by moderate sodium restriction, and levels increased with zero sodium intake. Therefore, sodium depletion can override the suppressive effect of energy restriction and, instead, increase the activity of the sympathetic nervous system, as reflected by plasma NE.