Effect of Acute Ethanol Intake and Hangover on the Levels of Plasma and Urinary Catecholamines and Lymphocytic β-Adrenergic Receptors

To determine whether acute ethanol administration affects the function of the adrenergic system the concentrations of plasma catecholamines and cyclic AMP (cAMP), the level of lymphocytic beta-receptors, the concentration of basal and isoproterenol-stimulated lymphocytic cAMP and the excretion of urinary catecholamine metabolites were studied in six healthy men. These parameters were also measured during the hangover, both under resting condition and during an anaerobic ergometer exercise. Acute intake of ethanol (1.5 g/kg body weight) had no statistically significant effect either on plasma adrenaline and noradrenaline concentrations or beta-adrenergic receptor levels. Ethanol consumption did neither change the urinary excretion of catecholamine metabolites (homovanillic acid, normetanephrine, metanephrine, and 3-methoxyhydroxymandelic acid). Exercise was associated with a 6-10-fold elevation in plasma adrenaline and noradrenaline concentrations and with a two- to threefold elevation on beta-adrenergic receptor levels. This effect of exercise was not modified by preceding alcohol intake and resulting hangover. These preliminary findings suggest that acute alcohol intake does not significantly alter the concentration and functioning of human beta-adrenergic receptors.     

Effect of age on acute regulation of beta-adrenergic responses in mononuclear leukocytes

We studied the acute regulation of beta-adrenergic receptors and cAMP production in mononuclear leukocytes from young and old human subjects. After one hour of supine rest, healthy young and elderly subjects had similar beta-adrenergic receptor density and cAMP responses to isoproterenol. After 10 min of standing, beta-adrenergic receptor density and cAMP response increased in the young subjects. Elderly subjects had a similar increase in cAMP responses after standing, but no change in beta-adrenergic receptor density. Lymphocyte subsets and percent monocytes were not altered by age or posture, suggesting that this was not an artifact of changes in cell populations. Incubation in vitro of cells from both groups with catecholamines, at concentrations comparable to those achieved in plasma after standing, resulted in enhanced isoproterenol-mediated cAMP responses, but no change in beta-adrenergic receptor density. These data suggest that acute regulation of adrenergic signaling is affected by age, mediated in part by catecholamines, and may be relevant in the study of acute cardiovascular regulation.     

Response of the beta-adrenergic system to maximal dynamic exercise in congestive heart failure secondary to idiopathic dilated cardiomyopathy

In congestive heart failure (CHF), prolonged exposure to high plasma catecholamine levels may reduce the responsiveness of the adrenergic system to physiologic stimuli. In healthy subjects, exercise is known to induce a rapid up-regulation of lymphocytic beta adrenoceptors. Lymphocytic beta-adrenoceptor density, lymphocytic basal and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) response, plasma catecholamine concentrations and plasma cAMP levels were studied during maximal ergometer exercise in 11 patients with CHF secondary to dilated cardiomyopathy and in 6 healthy control subjects. At rest, there was no difference in the lymphocytic beta-adrenoceptor levels between the patients and control subjects (48 +/- 3 vs 42 +/- 5 fmol/mg protein, respectively). However, the exercise-induced increase in lymphocytic beta adrenoceptors was attenuated in patients when compared with controls (26 +/- 6 fmol/mg protein [56%] vs 75 +/- 16 fmol/mg protein [204%], respectively, p less than 0.02). A subgroup of 4 patients with the lowest exercise capacity (peak oxygen uptake less than 12.5 ml/min/kg) had even more reduced up-regulation compared with the other 7 patients (13 +/- 1 fmol/mg protein [29%] vs 34 +/- 9 fmol/mg protein [71%], p less than 0.05). The lymphocytic cAMP response at rest and during exercise tended to be lower in patients compared with controls, but the differences did not reach statistical significance. The plasma levels of epinephrine and norepinephrine at rest were higher in patients compared with controls, but no difference was found in the exercise values. The plasma levels of cAMP correlated closely with plasma catecholamine levels at rest, but not during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of physical training on beta-adrenergic receptors in rat myocardial tissue

A diminished sympathetic activity has been related to training bradycardia seen at rest and during exercise. In order to evaluate if changes in heart adrenergic receptors can be one of the mechanisms by which the sympathetic responsiveness could be decreased by physical training, the number and affinity of beta-adrenergic receptors were determined in heart ventricular tissue of rats submitted to a 10-week running programme. Binding studies were done at different concentrations of (-)[3H] dihydroalprenolol (DHA) (0.5 to 14.4 nmol X litre-1) with ventricular membrane preparations from control and trained rats. Direct linear plot analysis revealed that physical training reduced the total number (1933 +/- 192 vs 2922 +/- 211 fmol X ventricles-1; P less than 0.01) density of beta-adrenergic receptors expressed either as fmol X mg-1 of membrane protein (34 +/- 3 vs 43 +/- 3; P less than 0.05) or as fmol X g-1 ventricle (1740 +/- 170 vs 2308 +/- 155; P less than 0.05). There was no significant change in the dissociation constant (3.11 +/- 0.14 vs 4.08 +/- 0.51 nmol X litre-1; P greater than 0.05). Basal plasma noradrenaline levels were not affected by training (116 +/- 18 vs 101 +/- 14 pg X cm-3; P greater than 0.10); however the adrenaline values were significantly higher in trained rats (91 +/- 16 vs 47 +/- 7 pg X cm-3; P less than 0.05). These data indicate that physical training induces changes at the level of beta-adrenergic receptors and this may partly explain the bradycardia seen in trained subjects and animals.     

Binding of adrenergic ligands to liver plasma membrane preparations from the axolotl, Ambystoma mexicanum; the toad, Xenopus laevis; and the Australian lungfish, Neoceratodus forsteri

The beta-adrenergic ligand iodocyanopindolol (ICP) bound specifically to hepatic plasma membrane preparations from the axolotl, Ambystoma mexicanum (Bmax, 40 fmol/mg protein (P) at free concentration above 140 pM; KD, 42 pM); the toad, Xenopus laevis (Bmax, 200 fmol/mg P at 1 nM; KD, 300 pM); and the Australian lungfish, Neoceratodus forsteri (Bmax, 100 fmol/mg P at 5 nM). For the lungfish, the Scatchard plot was curved showing two classes of binding site with KD's of 20 and 500 pM. Neither the alpha 1-adrenergic ligand prazosin nor the alpha 2-adrenergic ligand yohimbine bound specifically to hepatic membrane preparations from any of the three species. Several adrenergic ligands displaced ICP from hepatic membrane preparations of all three species with KD's of Axolotl--propranolol, 50 nM; isoprenaline, 600 nM; adrenaline, 10 microM; phenylephrine, 20 microM; noradrenaline, 40 microM; and phentolamine, greater than 100 microM; X. laevis--propranolol, 30 nM; isoprenaline, 100 microM; adrenaline, 200 microM; noradrenaline, 300 microM; phenylephrine, 1 mM; and phentolamine, greater than 1 mM; N. forsteri,--propranolol, 25 nM; isoprenaline, 1 microM; adrenaline, 20 microM; phenylephrine, 35 microM; noradrenaline, 600 microM; and phentolamine, 400 microM. These findings suggest that alpha-adrenergic receptors are not present in hepatic plasma membrane preparations from these three species and that the hepatic actions of catecholamines are mediated via beta-adrenergic receptors. The order of binding of the beta-adrenergic ligands suggests that the receptors are of the beta 2 type.     

Changes in plasma catecholamine concentrations in patients with coronary heart disease during pacing and physical exercise

To study the difference in sympathetic activity during pacing the right atrium or during physical exercise in patients with coronary heart disease, we investigated circulating plasma catecholamine concentrations in the coronary sinus and brachial artery radioenzymatically in 11 male patients with well documented coronary artery disease. Heart rate was increased stepwise 20 beats/min from 90 beats/min up to 150 beats/min by pacing the right atrium and physical exercise was performed by increasing work load stepwise by 25 from 25 up to 100 W on an ergometric bicycle. Plasma noradrenaline and adrenaline concentrations were increased significantly only during physical exercise. In addition, there was an increase in arterial-coronary sinus noradrenaline difference during graded physical exercise, whereas no further release of noradrenaline from the myocardium occurred during pacing. An enhanced cardiac sympathetic tone in patients with coronary heart disease is discussed. It is suggested that atrial pacing is not an adequate stimulus evoking an overall increase of cardiac and peripheral sympathetic tone.     

EFFECTS OF EXOGENOUS CATECHOLAMINES AND EXERCISE ON PLASMA MAGNESIUM CONCENTRATIONS

Catecholamines and physical exercise are known to influence the metabolism of several minerals in man, but the effects on magnesium (Mg) have been scarcely investigated. In the present study, infusion of adrenaline (5 micrograms/min for 30 min followed by 10 micrograms/min for 30 minutes) significantly reduced the plasma Mg levels in healthy males. This effect was abolished by simultaneous infusion of propranolol. Noradrenaline had no such effect. In order to stimulate endogenous catecholamine release healthy males carried out physical exercise in four different ways: ergometer bicycling at maximum load until exhaustion with and without oral beta-blockade, ergometer bicycling with stepwise increasing load until exhaustion, isokinetic maximal exercise with one leg, with blood sampling both from the venous effluent of the exercising leg and the opposite resting arm and long-term (60 min) steady state ergometer bicycling at approximately 65% of estimated maximum capacity. During short-term (less than 20 min) intense exercise (i.e. experiments 1-3) the plasma Mg concentrations were increased. This was probably due to a reduction of plasma volume and to an influx of Mg to the vascular pool. During long-term steady state exercise (experiment 4) the Mg levels were not significantly affected but decreased during the first hour of recovery. These results suggest that both the beta-adrenergic system and muscular activity by itself affect Mg homeostasis.     

The influence of single moderate exercise on the sympathetic nervous system activity in patients with essential hypertension

Sympathetic nervous system may play an important role in development and maintenance of hypertension. Its activity can be assessed by plasma levels of catecholamines, neuropeptide Y (NPY) and adrenergic receptor density. Hypertensive subjects may be more prone to reveal overactivity of sympathetic nervous system, for instance as a result of physical stress. The aim of the study was to determine the activity of sympathetic nervous system in young patients with newly recognized, untreated mild hypertension. INVESTIGATED GROUPS AND METHODS: The study was carried out in 22 patients (age 38.5 +/- 10.3 years) and 20 normotensive volunteers (age 38.5 +/- 8.6 years) as a control group, matched for sex. Density of alpha 2- and beta-adrenergic receptors using 3H-yohimbine and 125I-cyanopindolol respectively, total catecholamines and plasma renin activity using radioenzymatic assay, neuropeptide Y and aldosterone using radioimmunoassay were assessed in the blood taken in the supine position and after moderate bicycle ergometer exercise. RESULTS: Plasma concentration of NPY at rest did not differ between the groups, but increased significantly after exercise and was greater in hypertensive patients (p < 0.05). The density of alpha 2- and beta-adrenergic receptors at rest and after exercise in hypertensive subjects was unchanged when comparing to healthy individuals. The plasma concentrations of endogenous catecholamines, plasma renin activity and aldosterone level increase during exercise in both studied groups (p < 0.05). Aldosterone level was higher in hypertensive patients at rest (p < 0.05). There was a negative correlation between baseline aldosterone and NPY levels in hypertensive patients (r = -0.44, p < 0.05). CONCLUSION: Moderate exercise in hypertensive subjects causes the hyperactivity of sympathetic nervous system expressed as increase of NPY plasma level.     

Adrenocortical and adrenomedullary responses of fowl to treadmill exercise

Adrenomedullary and adrenocortical responses of 40-day-old cockerels to treadmill exercise (0.4 km/hr, 0 degrees incline) were determined. Plasma concentrations of adrenaline were increased above both resting and control levels (P less than 0.001) after 30 min exercise and continued to increase (P less than 0.01) until the cessation of exercise. Plasma noradrenaline and dopamine levels were increased after 60 min of exercise (P less than 0.01 and 0.05, respectively). The adrenaline component of the plasma catecholamine response increased significantly above that of noradrenaline (P less than 0.001). Plasma corticosterone levels were also increased (P less than 0.001) during exercise and were closely correlated with plasma adrenaline concentrations. Exercise depleted (P less than 0.01) adrenal stores of adrenaline, which were inversely proportional to plasma adrenaline concentrations (P less than 0.001). Neither adrenal noradrenaline nor dopamine were significantly correlated with their plasma levels. These results suggest that adrenocortical (corticosterone) and adrenomedullary (adrenaline) responses during exercise may occur in response to similar stimuli or may be interrelated.     

Enhanced exercise noradrenaline concentrations during propranolol treatment: a limiting factor in cardiac beta-adrenoceptor blockade

Treatment with beta-adrenoceptor blocking drugs may result in augmented plasma concentrations of noradrenaline during exercise. The effect of propranolol on exercise heart rate and its relationship to plasma concentrations of propranolol and noradrenaline were examined in 10 hospitalized volunteers following treatment with propranolol, in doses of 80 mg and 320 mg daily. Responses to submaximal treadmill exercise during propranolol treatment and following discontinuation of the higher dose were compared to pre-drug and post drug placebo values. Exercise noradrenaline was increased by 67% over baseline values by treatment with the 320 mg daily dose of propranolol; this increment was present at 4 h and returned to baseline by 16 h after drug administration. Augmentation of exercise noradrenaline was correlated with plasma propranolol concentrations; the threshold concentration for this effect was 10-fold higher than the threshold for reduction in exercise heart rate. The effect of propranolol on heart rate was blunted in relation to the augmentation of exercise noradrenaline (P less than 0.001). These relationships suggest that, in patients taking high doses of propranolol, drug induced augmentation of plasma levels of noradrenaline during exercise may have physiologic importance. Enhanced effects on adrenergic receptors could have clinical relevance in certain groups of patients.     

Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss)

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.     

Effect of Alcohol on Exercise-Induced Changes in Serum Glucose and Serum Free Fatty Acids

The effect of alcohol on exercise-induced changes in serum glucose, serum free fatty acids, and serum insulin was studied in healthy male volunteers by performing an exhaustive ergometer exercise: (1) followed by alcohol intoxication (induced by 1.5 g of alcohol/kg of body weight); (2) during alcohol intoxication (induced by 0.8 g of alcohol/kg of body weight); and (3) during hangover (13 hr after a dose of 1.5 g of alcohol/kg of body weight). Acute alcohol intake immediately before exercise inhibited the exercise-induced increase in mean serum glucose concentration and caused a mild decrease in serum glucose levels during recovery from exercise. Exercise during hangover also resulted in decreased glucose levels during recovery from exercise. Alcohol administration immediately before or after exercise inhibited the postexercise increase in mean serum free fatty acids concentration. This was not seen during hangover, when blood alcohol concentration had already reached 0. In conclusion, alcohol interferes with the metabolism of carbohydrates during and after anaerobic exercise by decreasing the availability of circulating glucose. Furthermore, during recovery from exercise, alcohol decreases the supply of free fatty acids for the body.     

Beta-adrenergic receptors and catecholamines in the rat heart during tourniquet trauma.

Tourniquet trauma produced a decrease in the noradrenaline content in the heart of the rats through the period of tourniquet application (up to 4 hr). In the same period, the content of adrenaline was significantly increased. This relationship between noradrenaline and adrenaline remained the same in the posttraumatic period. Parallel to the observed changes in the catecholamine content of the heart, a significant decrease in the number of the beta-adrenergic receptors (Bmax) and an increase in their affinity (a decrease in KD) was also found in the hearts of rats exposed to tourniquet trauma. These changes remained throughout the posttraumatic period, with one exception: no change 30 min after trauma has been observed. Reapplication of tourniquet was associated with a restoration of the beta-adrenergic receptors and complete survival of the animals. The decrease in the beta-receptors density after trauma might be due to down-regulation produced by increased concentration of adrenaline, a beta-receptor agonist. Meanwhile, some other factors, particularly ischaemia, might also contribute to the observed changes in the beta-adrenergic binding sites.     

Hormones regulating hepatic glycogenolysis in two chelonians use cyclic AMP, and not Ca2+, as intracellular messenger.

In teleosts, lungfish, amphibians, and a reptile, Amphibolurus nuchalis, hormonal stimulation of hepatic glycogenolysis is mediated by a rise in intracellular cyclic AMP concentration. In mammals, by contrast, the inositol trisphosphate/Ca2+/diacylglycerol signal transduction pathways are also involved. The present study describes the hormonal regulation of hepatic glycogenolysis in adult long-necked turtles, Chelodina longicollis, and hatchlings of the loggerhead turtle, Caretta caretta. Adrenaline and glucagon, but not neurohypophysial peptides, stimulated glycogenolysis, glycogen phosphorylase activity, and accumulation of cAMP in cultured liver pieces from either C. longicollis or C. caretta. The actions of adrenaline were blocked by a beta-adrenergic antagonist, propranolol, but were unaffected by an alpha-adrenergic antagonist, phentolamine. The effects of adrenaline were maintained in Ca(2+)-free medium containing EGTA, and were not mimicked by the Ca2+ ionophore, A23187. The beta-adrenergic ligand, [125I]iodocyanopindolol (ICP), specifically bound to membranes prepared from C. longicollis liver, with a calculated KD of 59 pM and a Bmax of 171 fmol/mg protein. The adrenergic ligands, propranolol, isoprenaline, adrenaline, phenylephrine, phenoxybenzamine, noradrenaline, and phentolamine displaced ICP with KD's of 50 nM, 5 microM, 22 microM, 140 microM, 180 microM, 250 microM, and 1 mM, respectively. The alpha-adrenergic ligands, prazosin and yohimbine, did not bind specifically to the membranes, although prazosin did bind to membranes prepared similarly from rat liver. Thus the glycogenolytic actions of adrenaline are mediated via beta-adrenergic receptors in liver from C. longicollis and C. caretta and alpha-adrenergic receptors may play no role in the control of hepatic metabolism in these chelonians.     

Respiratory function of catecholamines during the late period of avian development

To study the function of catecholamines in the late period of avian embryogenesis, the time course of plasma catecholamines, the release of catecholamines by hypoxia and finally the effect of adrenergic agents on blood parameters and on circulation were recorded. The experiments reveal a temporary increase in plasma adrenaline and noradrenaline shortly before internal pipping occurs. On the other hand a premature increase of plasma catecholamines is induced by hypoxia. Furthermore, treating the embryo with adrenergic agents such as adrenaline, noradrenaline and phenylephrine resulted in changes of blood gas parameters: increase of PO2, O2-saturation and negative base excess, decrease of PCO2 and HCO3-. In addition, exogenous adrenaline and noradrenaline released an increase in the blood flow and an enhanced hemoglobin content in the chorioallantoic membrane, but not in the kidneys. Finally, adrenaline caused a decrease of 2,3 DPG and an increase of lactate in the plasma. The data indicate that hypoxia, which is formed normally towards the end of embryogenesis, induces an increased secretion of catecholamines which in turn improves the blood gas status. In this way the embryo is protected from deleterious hypoxic damages. This conclusion has been derived from experiments, in which the release of catecholamines was blocked under hypoxia. Under these conditions a significant increase in the mortality rate was observed.     

Gonadotropin-releasing hormone increases plasma catecholamines and blood pressure in toads

Synthetic gonadotropin-releasing hormone (GnRH) was injected intravenously into conscious, adult toads (Bufo marinus) to elucidate the nervous and cardiovascular actions of the hormone. GnRH (0.001-1.0 nmol X kg-1) produced dose-dependent increases in mean arterial blood pressure and pulse pressure, beginning within 3 min after injection. These pressor responses to GnRH were specific to the hormone since they could be inhibited reversibly by [D-pGlu1, D-Phe2, D-Trp3,6]-GnRH. Arterial plasma concentrations of unconjugated catecholamines increased simultaneously with the rise in blood pressure following GnRH injection: the half-maximal pressor dose of GnRH (0.1 nmol X kg-1) caused a 3-fold increase in plasma noradrenaline and a 20-fold increase in plasma adrenaline concentrations. Pretreatment of toads with an alpha-adrenergic antagonist, prazosin, and a beta-adrenergic antagonist, propranolol, abolished the pressor responses to GnRH. We conclude that GnRH mobilizes catecholamines, which act through alpha- and beta-adrenergic mechanisms to raise blood pressure. Thus, endogenous GnRH or GnRH-like peptides may coordinate the pituitary, nervous and cardiovascular mechanisms which prepare toads for seasonal reproductive activity.     

The effects of LH, adrenaline and noradrenaline on testicular blood flow and plasma testosterone concentrations in anaesthetized rats

The acute effects of a 20 min constant rate intra-arterial infusion of LH and catecholamines on testicular blood flow and plasma testosterone concentrations were examined in sodium pentobarbitone anaesthetized rats. Ovine LH (2.5 microgram/min) elicited a 6-fold increase in testosterone concentration and a significant decrease of testicular vascular resistance. Noradrenaline and adrenaline (0.4 microgram/min) caused significant depressions in the plasma testosterone levels. The catecholamines induced no absolute changes in testicular blood flow but noradrenaline caused an increase in testicular vascular resistance. It was concluded that the catecholamine induced reductions in testosterone concentrations were not due to a vascular effect on the testis.     

Norepinephrine and thyrotropin effects on the thyroid in vitro: simultaneous stimulation of iodide organification and antagonism of thyroxine release

Norepinephrine (NE), which has previously been shown to inhibit TSH-induced T4 release by mouse thyroids in vitro, was found to stimulate iodide organification. The concentration of NE (6 X 10(-7) M) necessary to stimulate organification of iodide was 10 times less than the concentration (6 X 10(-6) M) required for inhibition of TSH-induced T4 release. Both actions of NE were exerted through an alpha-adrenergic receptor, since they were inhibited by phentolamine but not by l-propranolol. One milliunit of TSH maximally stimulated T4 release only, but larger amounts (100 mU) also stimulated organification. TSH stimulation of T4 release and organification was not affected by adrenergic antagonists and therefore was not mediated by adrenergic receptors. N6, O2-Dibutyryl cAMP and isobutylmethylxanthine, like TSH, stimulated T4 release. Their actions were inhibited by NE. However, both compounds, unlike TSH, failed to enhance organification in mouse thyroids. The effects of TSH and NE on the cAMP content of incubated mouse thyroids were also studied. TSH induced a prolonged increase in thyroidal cAMP during the 90-min incubation; this increase was unaffected by alpha- or beta-adrenergic antagonists. In contrast, NE (6 X 10(-5) M) produced a transient but significant increase in cAMP only within the first 5 min. Unlike the action of NE on organification, this short term stimulatory effect on cAMP production was mediated by a beta-adrenergic receptor, since it was blocked by l-propranolol but not by phentolamine. The following conclusions were reached: 1) stimulation of iodide organification and thyroid hormone release involves different sensitivity thresholds for TSH and NE; 2) TSH stimulation of iodide organification, hormone release, and cAMP formation is not exerted through adrenergic receptors; 3) NE stimulates organification and inhibits TSH-stimulated T4 release through alpha-adrenergic receptors, but stimulates cAMP production through beta-receptors; and 4) cAMP may not be the mediator of all TSH actions on the thyroid.     

Disturbed noradrenergic blood pressure control in normotensive members of hypertensive families.

The possible influence of a family history of hypertension on some variables of adrenergic blood pressure regulation was assessed. Blood pressure, heart rate, plasma renin activity, adrenaline and noradrenaline concentrations, and plasma or urinary electrolyte estimations did not differ significantly between two groups of normotensive subjects matched for age and sex with and without a family history of hypertension. Compared with subjects without a family history, however, an appreciably decreased pressor dose of infused noradrenaline, a distinct shift to the left in the relation between noradrenaline induced changes in mean arterial pressure and concomitant plasma noradrenaline concentrations, and an enhanced pressor response to given increases in plasma noradrenaline concentrations occurred in the group with a family history. These findings suggest that an imbalance between cardiovascular noradrenaline responsiveness and circulating noradrenaline is a common familial disturbance which could possibly predispose to the development of essential hypertension.     

Efficacy of oral sotalol in suppression of premature ventricular complexes and analysis of its beta-adrenergic blocking activity.

The efficacy of oral DL-sotalol in suppressing premature ventricular complexes was assessed by Holter recordings in 28 patients during short term (two weeks) and long term (two years) trials, and its beta-adrenergic blocking effects were evaluated by heart rate response to the Bruce treadmill stress test and plasma catecholamine increases upon active standing. Sotalol produced a significant decrease (more than 85%) in the number of premature ventricular complexes, during both short term (54%) of patients) and long term (39% of patients) trials. The doses employed in this study (320 mg/day) produced mild to moderate degrees of beta-adrenergic blockade as suggested by: a 20% reduction in the mean heart rate on 48 h Holter monitoring (P less than 0.0005); a 15 to 30% reduction in tachycardia induced by strenuous exercise; and a 12% reduction in standing-induced tachycardia. Under long term sotalol therapy the increase in plasma noradrenaline concentrations in response to active standing was not modified, but the increase in plasma adrenaline concentrations was greater than under baseline conditions (P less than 0.025). Both systolic and diastolic blood pressures significantly increased during long term sotalol administration (P less than 0.005 and P less than 0.025, respectively). However, blood pressure remained within the normotensive range during sotalol therapy. It was concluded that sotalol provides, at effective antiarrhythmic doses, a satisfactory level of beta-adrenergic blockade which during standing was associated with significant changes in adrenaline plasma increments.(ABSTRACT TRUNCATED AT 250 WORDS)