Circadian fluctuation of plasma epinephrine in supine humans.

Previous studies have demonstrated circadian fluctuations of systemic catecholamines in man. However, methodological differences and conflicting results with epinephrine are apparent. In the present study, plasma and urinary epinephrine and norepinephrine and plasma cortisol were studied in healthy young adult males over 24 hr with 20 min plasma sampling and EEG monitoring of sleep. Plasma epinephrine did not have a circadian variation in supine subjects. Urinary epinephrine levels and small urinary circadian variations were increased by normal posture and activity. Sleep and sleep stage were not associated with different plasma epinephrine levels, and no ultradian fluctuation was observed. Levels of norepinephrine and cortisol were normal. Based on all studies to date, it appears that basal plasma epinephrine has either a very small amplitude or no circadian rhythm, but that changes in posture and activity or the rest/activity cycle may modify this pattern.

Cholecystographic agents and sulfobromophthalein inhibit the binding of L-thyroxine to plasma membranes of rat hepatocytes.

Cholecystographic agents and sulfobromophthalein (BSP) cause a major discharge of labeled T4 from the liver in man in vivo. In the present study we sought to determine if this discharge is partially due to inhibition of T4 binding to plasma membrane sites. Plasma membranes were isolated from hepatocytes of female Sprague-Dawley rats, and 5'-nucleotidase levels were measured to demonstrate plasma membrane viability. Specific binding of T4 (Ka, 1.01 X 10(8) M) was confirmed by displacement of labeled T4 by unlabeled hormone (10(-10)-10(-5) M). Displacement of labeled hormone was also produced by addition of tyropanoate, iopanoate, ipodate, or BSP. At 5-mM concentrations of inhibitor, the Ka for T4 declined to 4.00 X 10(7) M with BSP, 5.07 X 10(7) M with ipodate, 5.62 X 10(7) M with tyropanoate, and 7.43 X 10(7) M with iopanoate. Thus, a portion of the discharge of hepatic T4 after administration of these agents may be due to competitive inhibition of binding to plasma membrane sites.

Evaluation of plasma 3-methoxy-4-hydroxyphenylglycol.

A high-performance liquid chromatographic (HPLC) assay suitable for the evaluation of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 1-ml aliquots of plasma is presented. Preparatory steps include extraction into ethyl acetate and minicolumn chromatography. Recoveries are monitored with [3H]MHPG. The HPLC procedure utilizes a C18 column, isocratic elution and amperometric detection. The assay was checked against a gas chromatographic-mass spectrometric procedure; the two procedures correlated well with a correlation coefficient of 0.99. Intra-assay reproducibility was 5.4%, inter-assay reproducibility 10.7%. Immediate changes in the orthostatic position did not affect the plasma MHPG concentration. Based on 22 normal controls the daytime plasma MHPG level was 2.98 +/- 0.66 ng/ml (mean +/- S.D.).

Endocrine and cardiovascular responses during phobic anxiety.

In vivo exposure therapy for phobias is uniquely suited for controlled studies of endocrine and physiologic responses during psychologic stress. In this study, exposure therapy induced significant increases in subjective anxiety, pulse, blood pressure, plasma norepinephrine, epinephrine, insulin, cortisol, and growth hormone, but did not change plasma glucagon or pancreatic polypeptide. Although the subjective and behavioral manifestations of anxiety were consistent and intense, the magnitude, consistency, timing, and concordance of endocrine and cardiovascular responses showed considerable variation.

Urinary catecholamines and mitral valve prolapse in panic-anxiety patients.

Free norepinephrine and epinephrine were measured in two consecutive 12-hour urine collections gathered during normal activity and sleep from 23 panic-anxiety patients and 9 normal subjects. Mitral value prolapse (MVP) was found in 7 of 20 patients who had echocardiograms. Mean nighttime norepinephrine and epinephrine excretion in panic-anxiety patients without MVP was significantly higher than that of control subjects, and was significantly higher than that of anxiety patients with MVP. In the daytime, all groups had higher catecholamine (CA) levels, but the differences between the groups were less pronounced. Medication significantly relieved symptoms and was associated with decreased CA levels. Elevated basal CA levels may characterize the subgroup of panic-anxiety patients who do not have MVP.

Adrenergic function in patients with panic anxiety.

Increased beta-adrenergic receptor sensitivity could account for many aspects of panic disorder. We tested this hypothesis by comparing 14 patients with six normal control subjects. The controls and eight patients had 14 blood samples taken, and heart rate and BP measured, during a four-hour protocol that included supine rest, a posture and isometric exercise stimulus, and a series of up to seven logarithmically increasing bolus intravenous doses of isoproterenol hydrochloride. The other six patients were studied only at rest. Patients had markedly elevated resting heart rate, substantially elevated levels of plasma epinephrine, cortisol, and growth hormone, mildly elevated plasma norepinephrine levels, and decreased heart rate responses to isoproterenol. These results suggest that beta-adrenergic receptor response is not increased, and may be decreased, in patients with panic disorder. Receptor down-regulation could result from the increased adrenergic function that these patients demonstrate, even in the absence of panic attacks.

Effects of cholecystographic agents and sulfobromophthalein on binding of thyroid hormones to serum proteins.

A number of interactions between thyroid hormones and cholecystographic agents have previously been demonstrated. In the present study we show that cholecystographic agents also interfere with the binding of thyroid hormones to serum proteins. A commercial kit (Tri-Tab) was used in which the uptake of labeled hormone from serum by a silicate adsorbent tablet is measured. In the presence of cholecystographic agents or sulfobromophthalein (BSP), the amount of labeled hormone bound to adsorbent increased in a dose-dependent fashion, reflecting displacement from protein-binding sites. The order of potency was BSP greater than ipodate greater than iopanoate greater than tyropanoate. Displacement of hormone was confirmed by a second methodology in which graded amounts of unlabeled T4 were added to the system. This allowed a Scatchard analysis to be performed for binding sites on T4-binding globulin. The cholecystographic agents and BSP caused displacement of the Scatchard slopes, again demonstrating interference with binding to serum protein sites. A method is described in which the change in Scatchard slope produced by an inhibitor is employed to compute the association constant between T4-binding sites on T4-binding globulin and the inhibitors. The values were: BSP, 14.6 X 10(3) M-1; ipodate, 4.7 X 10(3) M-1, iopanoate, 2.2 X 10(3) M-1; and tyropanoate, 0.1 X 10(3) M-1. Because of these relatively low values and the rapidity with which these agents are normally cleared from serum, it seems likely that effects on free hormone levels would be transient and of small magnitude during routine cholecystography. Also, ipodate, in the 1 g/day dose that has been employed experimentally to treat hyperthyroidism, should have a negligible effect on protein binding. On the other hand, when high levels of these compounds are used in experimental settings to study other aspects of thyroid hormone metabolism, changes in protein binding can occur and confound interpretation of results.

In vivo platelet aggregation and plasma catecholamines in acute myocardial infarction.

In vivo platelet aggregation assessed with the Filtragometer and potential correlates were compared among (1) patients with acute myocardial infarction (AMI), (2) normal controls, (3) patients with acute chest pain in whom AMI was eventually ruled out (ROMI), and (4) chronic outpatients (Cardiac Clinic group) with a history of myocardial infarction and/or angina pectoris. The measure was independent of sex, age, platelet count, immediate food intake, serum cholesterol, and triglyceride levels. The AMI group showed higher in vivo platelet aggregation than any of the other three groups (p less than 0.01). Least in vivo aggregation was seen in the normal group. Despite lack of correlation with the platelet aggregation measure, plasma epinephrine and norepinephrine showed statistically significant differences between the AMI and each of the other three groups. Our data support an association between platelet function and AMI, although not necessarily a cause and effect relationship.

The role of sympathetic activity in normal renin essential hypertension.

Understanding the connection between sympathetic activity and essential hypertension is still rudimentary. We studied interrelationships of plasma catecholamines, plasma renin activity (PRA), aldosterone, sodium intake, and therapeutic response of 20 normal renin hypertensives. Based on plasma norepinephrine (NE), this population fell into two distinct subsets. The 11 patients in the "normal" NE subset had a basal NE of 257 +/- 49 pg/ml (vs 250 +/- 62 pg/ml in normotensives), while nine patients in the "high" range NE group averaged 522 +/- 125 pg/ml. Both NE subsets showed significant correlation between mean arterial pressure (MAP) and NE. Only the "normal" NE subset showed significant correlation between MAP and PRA, and MAP and aldosterone. Correlations between changes in Na+ excretion and NE, PRA, and aldosterone were all negative and statistically significant. Blood pressure was controlled in eight of 11 "normal" NE patients but only in one of nine "high" NE patients by restriction of Na+ intake and/or use of a diuretic.