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Biomedical subjects

M G Ziegler

Publications and source records attributed to M G Ziegler.

At least 163 records · Page 9Linked to original sources
PubMed1983

Fenfluramine lowers plasma norepinephrine in overweight subjects.

The effect of fenfluramine on sympathetic nervous system activity was determined in 12 normotensive, obese men. Supine plasma norepinephrine (NE) concentrations decreased (p less than 0.001) from pretherapy levels (298 +/- 39 pg/ml) after one (166 +/- 30 pg/ml) and four weeks (171 +/- 28 pg/ml) of fenfluramine (60 mg daily). Fenfluramine did not alter the sympathetic nervous system responses to orthostasis or exercise. Fenfluramine-induced decreases in heart rate (72 +/- 3 to 67 +/- 4 beats/min, p less than 0.01) and mean arterial blood pressure (90 +/- 2 to 81 +/- 2 mmHg; p less than 0.005) were observed after only one week of therapy despite no significant change in body weight. We conclude that fenfluramine may be a useful agent in the treatment of patients with sympathetic hyperactivity. The effects of fenfluramine on given subsets of patients and control subjects are also defined.

Adult↗
PubMed1983

Effect of clonidine on sympathetic nervous system activity in patients with essential hypertension.

This study analysed the effects of both seven and 30 days of treatment with clonidine on heart rate, blood pressure (BP), plasma norepinephrine (NE) levels and dopamine-beta-hydroxylase (DBH) activity at rest and after standing in seven patients with essential hypertension. The patients and 10 age-matched normotensive control subjects were evaluated under medication-free baseline conditions; the hypertensive patients were then given clonidine 0.1 mg twice daily. Baseline plasma NE and DBH levels were similar between the groups. Seven and 30 days of clonidine therapy reduced blood pressure (p less than 0.001) and NE concentrations (p less than 0.05) significantly. Clonidine did not effect the percent increase in NE induced by standing and was not associated with orthostatic hypotension. The blood pressure lowering effects of clonidine appear related to the centrally mediated and/or direct suppression of peripheral noradrenergic activity, indicating the utility of clonidine in cases of hypertension were the sympathetic nervous system (SNS) is hyperactive. Clonidine may also prove especially useful in cases where the initial pharmacotherapy (such as a diuretic) causes activation of the SNS.

Adult↗
PubMed1982

Plasma norepinephrine and dopamine-beta-hydroxylase activity in schizophrenia.

Plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity may be altered by changes in posture, pulse rate, and BP. Twenty-three drug-free schizophrenic, ten schizoaffective, and 24 normal control subjects, and a separate group of eight schizophrenic patients treated with chlorpromazine hydrochloride and haloperidol comprised the sample. Drug-free schizophrenic patients showed higher plasma NE levels while standing and higher pulse rates when supine and standing than normal subjects. Following chlorpromazine therapy, but not following haloperidol treatment, plasma NE level increased with patients supine and standing, pulse rate increased with patients standing, and systolic BP decreased with patients standing. These findings suggest (1) a decreased peripheral alpha-adrenergic postsynaptic receptor sensitivity in schizophrenia and (2) a peripheral alpha-adrenergic blocking mechanism in chlorpromazine-induced hypotension.

Adult↗
PubMed1982

Hypermetabolic low triiodothyronine syndrome of burn injury.

The free tetraiodothyronine index (FT4I) and free triiodothyronine index (FT3I) in burn patients represented the serum levels of free (dialyzable) T4 and free T3, respectively. FT4I and FT3I were lower with greater burn size and were lower in nonsurvivors than expected for the burn size. there was no compensatory elevation of basal or releasing hormone-stimulated thyrotrophin (TSH) concentrations. Reverse T3 was higher with greater burn size. T3 treatment restored FT3I but did not affect mortality or resting metabolic rate (MR) measured in survivors, compared with placebo therapy. Whereas the hypermetabolic response to burn injury appeared t be independent of thyroid hormones, MR was correlated positively with burn size and with elevated plasma norepinephrine and epinephrine concentrations for several weeks after injury. Lack of augmented TSH concentrations, absence of low plasma reverse T3, and presence of hypermetabolism suggest that the reduced plasma free T3 does not indicate functional hypothyroidism, but may represent an adaptation to the assumption of metabolic control by the sympathetic nervous system.

Adolescent↗
PubMed1982

Analysis of adrenergic effects of the anesthetics Inactin and alpha-chloralose.

Renal and systemic adrenergic system responses were examined and compared under conditions of Inactin, a barbiturate, and alpha-chloralose anesthesia in hydropenic Munich-Wistar rats. Base-line plasma norepinephrine and other catecholamine levels were higher in Inactin-anesthetized rats. Norepinephrine was infused to raise blood pressure 15-20 mmHg above base line and plasma norepinephrine was again significantly higher with Inactin. In another group, angiotensin II was infused into the cerebral lateral ventricle in both Inactin- and alpha-chloralose-anesthetized rats, a method of stimulating centrally activated adrenergic output. After central stimulation, mean arterial pressure increased only in alpha-chloralose-anesthetized rats. Micropuncture studies examining systemic and glomerular hemodynamics were performed in alpha-chloralose- and Inactin-anesthetized rats before and after the infusion of phentolamine, an alpha-adrenergic antagonist. Infusion of phentolamine decreased mean arterial pressure to a significantly greater extent in the Inactin-anesthetized rats, suggesting a greater base-line systemic alpha-adrenergic activity with Inactin anesthesia. However, renal afferent and efferent arteriolar resistances were not significantly different after phentolamine, and any trend for resistances to decrease could be explained by autoregulation. Inactin increases systemic adrenergic activity, but renal vascular resistances are not significantly affected by this increased activity.

Anesthetics↗
PubMed1982

Effect of nerve growth factor on catecholamine metabolism in a human neuroblastoma clone (SY5Y).

The neuroblastoma line SK-N-SH-SY5Y (SY5Y) is a thrice subcloned nearly diploid clonal line of human origin. When grown in 15% fetal calf serum in Ham's F-12 medium as herein described, SY5Y has neuroblast-like properties in its undifferentiated state. Treatment with nerve growth factor results in morphological and physiological differentiation not unlike that elicited by nerve growth factor in sympathetic ganglia primary cultures. Careful examination of catecholamine synthesizing enzyme specific activities and catecholamine concentrations in nerve growth factor-treated SY5Y cells showed a small elevation of tyrosine hydroxylase, no change in dopamine-beta-hydroxylase or in dopamine or norepinephrine intracellular concentrations. This is consistent with the interpretation that nerve growth factor acts as a permissive or trophic factor, and not necessarily as an instructive or specifying factor in this system.

Catecholamines↗
PubMed1982

High plasma norepinephrine levels in patients with major affective disorder.

The authors found that patients with major affective disorder had higher levels of plasma norepinephrine and higher pulse rates (tachycardia) than healthy control subjects, but their blood pressures were normal. These measurements were similar in all three subgroups of patients with affective disorder--manic, bipolar depressed, and unipolar. Because norepinephrine is the primary neurotransmitter of the sympathetic nervous system, these data suggest sympathetic hyperactivity in the major affective disorders. This conclusion is compatible with recent speculation based on the effect of antidepressants on noradrenergic receptors and a failure of alpha-receptors to downregulate normally in patients with major affective disorder.

Adult↗
PubMed1982

Increased cerebrospinal fluid norepinephrine in essential hypertension.

Studies in man and animals suggest increased central noradrenergic activity in hypertension. We can now measure norepinephrine (NE) in cerebrospinal fluid (CSF) accurately and this should provide an index of central noradrenergic activity. NE in CSF is very labile and altered by anxiety, stress, drugs, sodium balance and other factors. When these factors are controlled, NE in CSF appears elevated in essential hypertensives, particularly among young patients. Neurologic diseases that alter NE in CSF cause parallel alterations in blood pressure. Increased central noradrenergic activity is reflected in CSF NE levels and may cause some forms of hypertension.

Age Factors↗
PubMed1982

Adrenergic receptors in human and experimental pheochromocytoma.

Radioligand binding to adrenergic receptors has become an important technique for identification and quantitation of these receptors. In this article we review our recent findings using subtype-selective radioligands for studying alpha 1 (e.g., [3H]prazosin) and alpha 2 (e.g. [3H]yohimbine) receptors in human platelets and rat renal cortical membranes, and we report new results on changes in adrenergic receptors of patients and animals with pheochromocytoma. Five patients with pheochromocytoma were tested prior to surgery. The number of alpha 2-adrenergic receptors on platelets from these patients and the affinity of these receptors for [3H]yohimbine were similar to values for control subjects. In rats with a transplantable pheochromocytoma we found a 50-fold increase in plasma norepinephrine levels. The number of renal cortical beta-adrenergic receptors (identified using [125I]iodohydroxybenzylpindolol) and alpha 1-adrenergic receptors were decreased while the number of alpha 2-adrenergic receptors did not change. Receptor affinities for radioligands were unaltered in animals with pheochromocytoma. These findings indicate that pheochromocytoma is associated with selective decreases in the number of renal beta- and alpha 1-adrenergic receptors without changing alpha 2-adrenergic receptor number or affinity. Furthermore, the number and affinity of alpha 2-adrenergic receptors are not altered in platelets of patients with pheochromocytoma. We conclude that down regulation (an agonist-mediated decrease in receptor number) occurs in vivo for some, but not all, types of adrenergic receptors.

Adolescent↗
PubMed1981

Differential effects of DL-propranolol on norepinephrine in cerebrospinal fluid and plasma.

Acute administration of DL-propranolol (5 mg/kg, subcutaneous) to cats caused a significant increase in cerebrospinal fluid (CSF) norepinephrine and a significant decrease in plasma norepinephrine. This increase in CSF norepinephrine is probably due to a reflex increase in central noradrenergic firing after beta blockade. The decrease in plasma norepinephrine reflects decreased sympathetic outflow. These results are consistent with the centrally mediated hypotensive effects of the drug.

Animals↗
PubMed1981

Origins of spinal noradrenergic pathways demonstrated by retrograde transport of antibody to dopamine-beta-hydroxylase.

Retrograde transport of antibody to dopamine-beta-hydroxylase (DBH) was used to locate the cells of origin of descending noradrenergic (and possibly adrenergic) pathways to the spinal cord. Following injections of DBH antibody into various spinal cord levels, cell bodies were immunocytochemically localized in brainstem nuclei known to contain noradrenergic neurons. These cell groups included the nucleus locus coeruleus, the nucleus subcoeruleus, the medial and lateral parabrachial nuclei, the Kölliker-Fuse nucleus, and the region dorsal and lateral to the superior olivary nucleus. Caudally, none of the noradrenergic cell groups of the medulla contained retrogradely labeled neurons. These findings indicate that the sources of spinal cord noradrenergic input are derived exclusively from the cells of the pons.

Animals↗
PubMed1981

Essential hypertension: central and peripheral norepinephrine.

The concentration of norepinephrine in cerebrospinal fluid from patients with essential hypertension is higher than that from healthy normal volunteers, but the concentrations of norepinephrine in plasma from these groups are similar. This finding indicates that central nervous system noradrenergic hyperactivity occurs in essential hypertension but apparently is not reflected in abnormal function of the peripheral sympathetic nervous system in these patients.

Adult↗
PubMed1981

The hyperactive child syndrome: peripheral sympathetic nervous system function and the effect of d-amphetamine.

We evaluated sympathetic nervous system function in medication-free hyperactive children by measuring plasma levels of norepinephrine (NE) and dopamine-beta-hydroxylase and then comparing the effects of two therapeutics doses of d-amphetamine to placebo in these patients. The medication-free hyperactive patients and controls had similar plasma NE levels and blood pressures while recumbent, and a similar increase in NE on standing, but the patients had a larger pressor response on standing. In the hyperactive patients d-amphetamine significantly increased blood pressure, pulse rate, and NE levels. The change in NE levels correlated with the change in amphetamine levels. The medication-free patients, when more anxious, had higher plasma NE levels.

Attention Deficit Disorder with Hyperactivity↗
PubMed1981

Effects of chronic digitalization on cardiac and renal Na+ + K+-dependent adenosine triphosphate activity and circulating catecholamines in the dog.

To extend our understanding of the mechanism of action of digitalis drugs, we studied electrocardiograms (ECGs), renal function, plasma concentrations of catecholamines, and myocardial and renal Na+ + K+-dependent adenosine triphosphate (Na+ + K+ ATPase) activity in chronically digitalized dogs. Five healthy, male, mongrel dogs received a therapeutic regimen of digoxin (0.1 mg/kg on day 1 in three divided doses followed by 0.025 mg/kg per day) orally for 2-4 months. This resulted in plasma digoxin concentrations of 1.1 to 4.7 ng/ml as determined by radioimmunoassay. Six control dogs received daily gelatin capsules by mouth. ECGs monitored throughout the study showed no changes. Digitalized dogs had elevated plasma norepinephrine concentrations (347 vs. 137 pg/ml in controls) and no change in plasma epinephrine concentrations. Digitalized dogs had elevated glomerular filtration rates (0.74 vs. 0.94 ml/min per g of kidney) without significant changes in renal handling of electrolytes and water. All of the above studies were done without the aid of restraining drugs or infusions. The animals were killed with an overdose of pentobarbital for in vitro studies. In digitalized dogs, microsomal Na+ + K+ ATPase-specific activity was 26 to 33% lower in the renal cortex, medulla, and papilla, and 46% lower in the cardiac left ventricle than in control dogs. Digitalization did not alter the osmolalities of renal tissues. We conclude that chronic reduction Na+ + K+ ATPase activity by one-third dose does not cause abnormalities in renal handling of electrolytes and water, and inhibition of Na+ + K+ ATPase in the left ventricular muscle by one-half is associated with no obvious ECG changes in the dog. Further, elevated plasma norepinephrine concentrations may contribute to both the therapeutic and the toxic effects of digitalis.

Animals↗
PubMed1981

Circulating catecholamines and sympathetic activity after head injury.

Plasma norepinephrine (NE) and dopamine beta-hydroxylase (DBH) levels were measured during the first 7 days after head injury in 48 patients. Blood pressure, pulse, temperature, and Glasgow coma score (GCS) were recorded at the time of sampling for each patient, and the relationships of these to NE and DBH were examined. In patients with multiple trauma, NE levels were usually elevated, regardless of the GCS. In patients with head injury alone, however, NE was proportional to GCS. Alert patients after a brief loss of consciousness (GCS, 14) had normal NE levels. Those in coma had levels as high as 7 times normal. Blood pressure, pulse, and temperature were found to be elevated proportionally to elevations in plasma NE in patients with head injury. The finding of elevated plasma NE in patients with severe head injury raises the possibility of adverse effects of sympathetic hyperactivity in patients with severe head injury, including hypermetabolism, cardiovascular abnormalities, and direct effects of catecholamines on the damaged central nervous system.

Blood Pressure↗
PubMed1980

Schizophrenia: elevated cerebrospinal fluid norepinephrine.

Concentrations of norepinephrine in cerebrospinal fluid are higher in schizophrenic patients, particularly in those with paranoid features, than in normal volunteer subjects of the same age. This observation supports recent reports of elevated concentrations of norepinephrine in specific brain areas adjacent to the cerebral ventricles of paranoid schizophrenic patients. Overflow of the amine from periventricular regions into the cerebrospinal fluid may reflect abnormally high release or diminished enzymatic destruction of norepinephrine in patients with schizophrenia.

Adult↗