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In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor densities (and binding affinities), measured with 3H-labelled yohimbine, and adrenaline-induced suppression of cyclic AMP contents did not differ among the three groups. Thus, in contrast to idiopathic autonomic failure, there is no generalized increase in adrenergic receptors in autonomic failure due to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo.

The muscarinic cholinergic antagonist 3H-quinuclidinyl benzilate was used to study muscarinic cholinergic receptors in the brain and the heart from triiodothyronine, thyroxine and 6-propyl-2-thiouracil treated rats. Scatchard analysis of the saturation binding studies revealed for each rat in both brain and heart tissue a single group of muscarinic cholinergic receptor binding sites of high affinity. The density and the affinity of muscarinic cholinergic receptors in brain and heart homogenates from treated rats were not different from values obtained in control rats with the exception of triiodothyronine treated rats which showed a slightly but significantly increased equilibrium dissociation constant in the brain homogenates. Furthermore, we observed that the density of the muscarinic cholinergic receptors in the brain was significantly lower in the month of August as compared to March-April, which suggests a seasonal variation. No similar change was observed in heart homogenates. Our results suggest that cardiovascular and central nervous symptoms in patients with thyroid diseases cannot be ascribed to changes in muscarinic cholinergic receptors.

We determined the circulating dopamine levels in 17 patients with insulin-dependent diabetes mellitus (IDDM), of whom eight had amenorrhoea (DM-AM) and nine were normally menstruating (DM). Seven non-diabetic women with normoprolactinaemic, normogonadotrophic secondary amenorrhoea (AM) and nine normally menstruating women (controls) were studied. In all subjects basal blood concentrations of free dopamine (f-DA), conjugated dopamine (c-DA), epinephrine (E), norepinephrine (NE), prolactin (PRL), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and oestradiol-17 beta were determined and all subjects, except for three AM patients, had a Metoclopramide test performed for measurements of f-DA, c-DA, PRL, LH and TSH. Plasma c-DA was significantly (p less than 0.05) increased in patients with amenorrhoea compared to the respective control groups. In diabetic patients c-DA levels were significantly (p less than 0.05) lower compared to controls. The ratio between basal f-DA and c-DA concentrations was significantly (p less than 0.01) higher in diabetic patients compared with non-diabetic patients. After Metoclopramide stimulation DM-AM patients showed a significant (p less than 0.05) rise in c-DA, whereas this was not seen in other groups. DM-AM patients had significantly (p less than 0.05) lower basal PRL and LH levels than DM patients and controls. In addition DM-AM patients had a significantly (p less than 0.05) lower PRL response to Metoclopramide compared with DM patients. There were no significant correlations between catecholamines and basal as well as Metoclopramide stimulated pituitary hormones. This study suggests that the abnormal pituitary hormone secretion in patients with amenorrhoea may in part be caused by an increased dopaminergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Microelectrode recordings of muscle nerve sympathetic activity and measurements of venous plasma noradrenaline have indicated increased sympathetic outflow during acute hypoglycaemia. Plasma volume reduction during hypoglycaemia, as evidenced by increasing peripheral venous haematocrit might underly the sympathetic activation. To study the effect of prevention of plasma volume reduction during hypoglycaemia, saline containing albumin was infused intravenously in healthy adult volunteers during hypoglycaemia. Hypoglycaemia was induced by an intravenous injection of soluble insulin in a dose of 0.15 IU/kg body weight. Peripheral venous plasma noradrenaline concentrations were identical in experiments without and with plasma volume substitution. Muscle nerve sympathetic activity increased to the same extent during hypoglycaemia with and without plasma volume substitution. It is concluded that increased plasma noradrenaline concentrations and enhanced muscle nerve sympathetic activity during insulin-induced hypoglycaemia in man are not consequences of plasma volume reduction.

An oral glucose load increased urinary albumin excretion significantly in six normal subjects (from a mean basal value of 4.6 microgram/min to 16.9 microgram/min at 30-90 min after oral glucose). Urinary excretion of beta-2-microglobulin did not change after oral glucose whereas urinary volume increased. Administration of the water vehicle did not increase albumin excretion. Oral glucose had no effect on urinary albumin excretion in six insulin-dependent diabetics. The effect of oral glucose was not identical to the changes observed after intravenous insulin because oral glucose urinary volume and did not change beta-2-microglobulin excretion whereas insulin decreased both parameters.

Previous studies indicate that the forearm venous plasma norepinephrine (NE) concentration is abnormally high in patients with duodenal ulcer. The aim of the present study was to examine the relationship between age and plasma NE concentration in patients with duodenal ulcer and controls. Eleven male patients with duodenal ulcer and 12 male control subjects were examined. Plasma NE concentration was approximately twofold greater in duodenal ulcer patients in both the resting seated position and during exercise than values obtained in controls (2 p less than 0.02, less than 0.05). There was a strong correlation between plasma NE and age in patients with duodenal ulcer but not in controls (r = 0.69, 2 p less than 0.05). Our results suggest that the increase in plasma NE with age is greater in patients with duodenal ulcer than in normal healthy subjects or in patients with minor surgical diseases. Patients with duodenal ulcer may have a higher functional age than healthy subjects.

Plasma renin activity (PRA), plasma noradrenaline concentration, heart rate, blood pressure, and clearances of para-aminohippurate and inulin were measured in twelve normal subjects (clearances in only three subjects) before and after 40 min of 60 degrees upright tilting. The tilting experiments were repeated after inflation of an anti-gravity suit to 60 mmHg on the lower extremities. Inflation of the anti-gravity suit caused an abolition of the postural PRA increase, a marked reduction of the postural increases in plasma noradrenaline and heart rate, and elimination of the decreases in pulse pressure, inulin and para-aminohippurate clearances and sodium excretion. The results suggest a decisive role of the sympathetic nervous system for postural renin increase, probably mainly activated by stretch receptors in the low-pressure cardiopulmoanry area.

Timolol of 0.5% was applied in 6 eyes prior to cataract extraction, while 7 eyes were not treated. Aqueous humor was drawn after retrobulbar analgesia with 2% lidocaine and analyzed for epinephrine and norepinephrine using a radioenzymatic assay. Epinephrine levels averaged 15.8 +/- 16.2 and 19.3 +/- 27.5 pg/ml in the timolol treated group and controls respectively. The corresponding values for norepinephrine were 1.59 +/- 0.55 and 1.87 +/- 0.90 ng/ml. These differences were not statistically significant. Norepinephrine levels in this study were somewhat higher than in previous reports of catecholamine levels in human aqueous humor and considerably higher than plasma levels of norepinephrine. There was no significant correlation between aqueous humor norepinephrine levels and age in the two groups combined. The mean norepinephrine levels for men and women in the two groups combined were 1.73 +/- 0.89 and 1.76 +/- 0.56 ng/ml. The difference was not statistically significant. Timolol resulted in a decrease in the intraocular pressure.

Nine patients with chronic obstructive lung disease underwent right heart catheterization. Mean pulmonary arterial pressure was elevated, but none of the patients had clinical signs of cardiac failure. Mean arterial oxygen saturation and carbon dioxide tension were 89% and 47 mmHg, respectively. Plasma noradrenaline (NA) concentration averaged 0.51 ng/ml and was inversely correlated to arterial oxygen saturation and mixed venous oxygen saturation, and positively correlated to arterial carbon dioxide tension and mean pulmonary arterial pressure. Oxygen inhalation did not change plasma NA significantly. Eight months later, plasma NA was increased (mean 0.89 ng/ml), as compared to the first determination (P < 0.02), and to a group of normal subjects (mean 0.26 ng/ml, P < 0.005). Inverse correlation to arterial oxygen saturation and direct correlation to arterial carbon dioxide tension were still present. Plasma adrenaline concentration was normal. The results point to enhanced sympathetic nervous activity in patients with chronic obstructive lung disease, probably caused by the deranged blood gases. The pulmonary haemodynamic changes and increased pulse rate may, at least partly, be due to enhanced sympathetic nervous activity.

Forty-year-old individuals with labile and with mild sustained essential hypertension, identified during a survey of a population born in 1936, were investigated. None had ever received antihypertensive treatment. In thirty-three individuals (26 M, 7F) with diastolic blood pressure (DBP) greater than or equal to 95 mmHg at the very first examination and in thirty-one (14 M, 17 F) randomly selected normotensive controls plasma noradrenaline concentration (PNAC) was measured at rest supine. In twenty-two patients (16 M, 6 F), with sustained diastolic hypertension (diastolic blood pressure greater than or equal to 95 mmHg on at least three different occasions) and in twenty-four (14 M, 10 F) normotensive controls PNAC and plasma renin concentration (PRC) were measured supine at rest and again 2 h after furosemide and ambulation. Basal and acutely stimulated values for PNAC and PRC were identical in hypertensive and normotensive individuals. A close correlation between PNAC and PRC after acute stimulation (r = 0.77, P0.001) as well as between the absolute changes from resting to acutely stimulated values (r = 0.72, P0.001) were found in the hypertensive individuals. It is concluded that sympathetic nerve activity, as defined from measurements of plasma noradrenaline concentration, is similar in young patients with mild hypertension and in normotensive controls. We propose that the discrepancies found in the literature might be related to a lack of comparability between hypertensive and normotensive individuals studied, as far as the source of study populations is concerned.