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.     

Effect of a benzodiazepine (alprazolam) on plasma epinephrine and norepinephrine levels during exercise stress

To determine whether a benzodiazepine central nervous system depressant, alprazolam, inhibits sympathetic discharge during exercise stress, 11 healthy men, aged 21 to 35 years, performed symptom-limited treadmill tests before and on the third day of drug therapy (0.5 mg 3 times daily). Plasma epinephrine and norepinephrine levels were measured at rest and at 8 minutes, 11 minutes and maximal exercise. Owing to catheter malfunction during vigorous exercise, paired samples could be obtained from only 8 subjects at 8 minutes and from only 4 subjects at 11 minutes of exercise. During drug treatment, the plasma epinephrine level was lower at rest (30 +/- 4 vs 53 +/- 7 pg/ml, p less than 0.01), and at 8 minutes (60 +/- 13 vs 117 +/- 19 pg/ml, p less than 0.01), 11 minutes (120 +/- 39 vs 193 +/- 52 pg/ml, p less than 0.05), and maximal exercise (520 +/- 125 vs 970 +/- 324 pg/ml, p = 0.13). Plasma norepinephrine was unchanged at rest (452 +/- 57 vs 413 +/- 45 pg/ml) but lower at 8 minutes (730 +/- 75 vs 886 +/- 82 pg/ml, p less than 0.01), 11 minutes (1,077 +/- 197 vs 1,447 +/- 301 pg/ml, p less than 0.05) and at maximal exercise (3,453 +/- 487 vs 5,590 +/- 1,100 pg/ml, p = 0.09). Exercise duration (17 +/- 1 and 17 +/- 1 minutes) was unchanged on drug. Thus, alprazolam reduces the plasma catecholamine response to exercise stress, possibly by inhibiting centrally mediated sympathetic discharge. Blunting of sympathetic activation may be beneficial in cardiac disorders in which increased sympathetic tone is potentially deleterious.     

Plasma norepinephrine and epinephrine in acromegaly.

Plasma norepinephrine and epinephrine concentrations were measured, in the supine resting position and in response to standing, in 10 unselected patients with active acromegaly, in 2 effectively treated acromegalic patients with normal serum growth hormone concentrations and in 15 nonacromegalic normal subjects. Plasma catecholamine concentrations were not significantly related to serum growth hormone levels or to the diastolic blood pressure in the acromegalic patients. Mean (+/- SE) plasma norepinephrine concentrations rose from 211 +/- 28 pg/ml supine to 501 +/- 65 pg/ml after 10 minutes standing in the active acromegalic patients and from 210 +/- 20 pg/ml supine to 502 +/- 54 pg/ml after 10 min standing in the normal subjects. Corresponding plasma epinephrine concentrations were 33 +/- 6 and 60 +/- 14 pg/ml in the acromegalics and 57 +/- 7 pg/ml in the normals. Thus, no abnormality in basal or stimulated plasma catecholamine concentrations was found in acromegalic patients.     

Effects of intrahypothalamic injection of quinolinic acid on anterior pituitary hormone secretion in the unanesthetized rat

Bilateral intrahypothalamic injections of the brain metabolite quinolinic acid (QUIN) were made in an attempt to examine its effects on the secretion of LH, PRL, GH and TSH. Quin, a neuroexcitatory amino acid with close structural similarities to glutamate, kainate and N-methylaspartate, was infused into unanesthetized male rats, the animals sacrificed 7.5 min later, and serum hormone concentrations determined by radioimmunoassay. QUIN caused surges in LH, PRL and GH release (316, 607 and 1,134% of control, respectively, at 50 micrograms QUIN) without affecting the serum concentrations of TSH. At lower doses, a preferential effect of QUIN on PRL release was observed. All QUIN-induced hormonal changes were inhibited by concomitant administration of the specific antagonist (-)-2-amino-7-phosphonoheptanoic acid, indicating the presence of QUIN-sensitive receptors on neurons which are intimately associated with endocrine regulation. Moreover, because QUIN-treated animals exhibited behavioral signs of seizure activity and neuroendocrine dysfunction has been reported to occur in human convulsive disorders, the data are also of interest in view of a possible mechanistic link between epileptic phenomena and hormone secretion.     

Age differences in the plasma clearance mechanisms for epinephrine and norepinephrine in humans

There is an age-related increase in plasma norepinephrine (NE) in humans that is due to both an increase in NE appearance into plasma and a decrease in plasma NE clearance. However, previous studies demonstrated no difference in plasma epinephrine (EPI) in young and old subjects, and the effect of aging on plasma EPI appearance and clearance is unclear. To study age differences in basal NE and EPI metabolism we infused eight young (aged 19-26 yr) and eight old (aged 64-74 yr) normal subjects with [3H]NE or [3H]EPI (15 microCi/m2 bolus dose plus 0.35 microCi/m2/min for 50 min) to achieve steady state conditions on separate days. The old subjects had higher arterialized plasma NE levels [mean, 217 +/- 13 (+/- SE) vs. 149 +/- 12 pg/mL; P less than 0.005] and plasma NE appearance. In contrast, neither plasma EPI levels (98 +/- 8 vs. 104 +/- 10 pg/mL; P = NS) nor EPI appearance rates were different in the old and young subjects. The plasma clearance rates of EPI and NE were nearly identical in the young subjects (1.63 +/- 0.14 vs. 166 +/- 0.09 L/min X m2; P = NS). Plasma NE clearance was lower in the old compared to the young subjects (1.38 +/- 0.06 vs. 1.64 +/- 0.10 L/min X m2; P less than 0.05) and was lower than EPI plasma clearance in the same subjects. Although NE and EPI can be removed by both neuronal and nonneuronal uptake mechanisms, and mean plasma clearance values for NE and EPI are the same in the young, the age-related decline in catecholamine clearance is specific for NE. This finding implies a differential effect of age on a catecholamine removal mechanism that is specific for NE.     

A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue.

A double-isotope, radioenzymatic assay for measuring dopamine, norepinephrine, and epinephrine in one sample is described. The assay procedure includes incubation, solvent extraction, and thin-layer chromatography. Dopamine, norepinephrine, and epinephrine were incubated with catechol-O-methyl transferase (COMT) and [3H]S-acenosyl methionine ([3H]SAM) and were converted to the O-methylated tritiated derivatives: [3H]methoxytyramine, [3H]normetanephrine, and [3H]metanephrine, respectively. After several extraction steps the O-methylated products were purified by means of two-dimensional, thin-layer chromatography using silica gel. The thin-layer chromatographic system resulted complete separation of the three O-methylated compounds with an overlap of only 1-2%. The assay was linear from 0 to 5 ng for each catecholamine and had a sensitivity of 10-30 pg. The addition of large amounts of plasma reduced the activity of COMT, but increasing the magnesium concentration in the incubation mixture and the addition of EGTA to plasma samples improved the recoveries. Each sample was corrected for losses incurred during extraction and chromatography by using [14C]methoxytyramine, [14C]normetanephrine, and [14Ci1metanephrine that were added at the end of incubation. Several catechol compounds known to be O-methylated by COMT were examined for crossreactivity. Of the substances tested, only dihydroxyphenylalanine (DOPA) exhibited cross-reactivity. However, the apparent 30% cross-reactivity of DOPA with dopamine was due to the presence of decarboxylase activity in the COMT preparation. As little as 50 mul of trunk plasma from decapitated rats was sufficient for the determination of the three catecholamines.     

Fluid temperature and volume dependence of the dissociated plasma epinephrine and norepinephrine response to drinking

The ingestion of cold fluids results in a rise in plasma norepinephrine (NE) and a fall in plasma epinephrine (E). To assess the relative roles of fluid volume and temperature in mediating this dissociated sympathetic response to drinking, NE and E levels were measured on 3 separate occasions in 10 men before and after ingestion of either 750 ml distilled water at 4 C, 750 ml at 25 C, or 150 ml at 4 C. An increase in plasma NE occurred after drinking 750 ml water at both 4 C and 25 C. Levels rose during ingestion of fluid and fell again when drinking was completed, consistent with a sympathetic response to deglutition. There was no change after 150 ml at 4 C. In contrast, plasma E fell after the men drank 750 ml water at 4 C, but it did not change after they drank 750 ml water at 25 C or 150 ml at 4 C. The fall was maximal 10 min after drinking was completed and levels remained depressed for a further 30 min. These findings suggest that the fall in E is temperature dependent and is a response to the presence of cold fluid in the stomach rather than to deglutition. We conclude that the dissociation of the plasma NE and E response after drinking cold fluids is therefore a result of independent and contrasting influences of, respectively, the volume and temperature of the fluid ingested.     

The effect of norepinephrine on insulin secretion and glucose effectiveness in non-insulin-dependent diabetes

It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([K_G] SAL v NE, 0.73 ± 0.06 v 0.61 ± 0.06 × 10⁻² · min⁻², P < .05), (2) no reduction in Si (2.33 ± 0.8 v 2.62 ± 0.9 × 10⁻⁴ · min⁻¹/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 ± 0.19 v 1.01 ± 0.16 × 10⁻³ pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 ± 0.08 v 1.63 ± 0.2 × 10⁻² · min⁻¹ P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 ± 0.13 v 1.30 ± 0.33 × 10⁻² · min⁻¹, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.     

Effects of epinephrine, norepinephrine, and dopamine on gonadotropin-releasing hormone-induced secretion of luteinizing hormone in vitro

Recent evidence indicates that catecholamines may directly alter anterior pituitary function. In the present study, an in vitro perifusion system was used to investigate whether catecholamines affect the gonadotrope. Pituitary tissue from castrated ram lambs was incubated in the presence of epinephrine (EPI), norepinephrine (NE), or dopamine (DA). During a 2-h treatment period, neither DA (10(-8) M), NE (10(-7) M), nor EPI (10(-7) - 10(-9) M) significantly affected basal LH secretion. In contrast, the LH response to a subsequent 10(-10) M GnRH challenge was significantly potentiated by NE and EPI. NE increased the amount of LH secreted in response to GnRH 14 +/- 1.1% (P less than 0.01). Likewise, 10(-7), 10(-8), and 10(-9) M EPI resulted in 22 +/- 1.4% (P less than 0.001), 13 +/- 1.2% (P less than 0.001), and 6 +/- 1.3% (P less than 0.03) increases, respectively. The stimulatory effect of 10(-7) M EPI was blocked by pretreatment with propranolol (a beta-adrenergic blocker), but not with phentolamine (an alpha-adrenergic blocker). The beta-adrenergic agonist isoproterenol enhanced GnRH-induced LH secretion 46 +/- 1.5% (P less than 0.001), but had no effect on basal LH release. DA had no effect on LH secretion; however, it inhibited PRL release 24 +/- 0.9% (P less than 0.001). Neither NE, EPI, nor isoproterenol had any effect on PRL secretion. These results suggest that EPI, acting by a beta 2-adrenergic receptor, modulates the pituitary gonadotrope's response to GnRH.