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Biomedical subjects

C R Lake

Publications and source records attributed to C R Lake.

At least 145 records · Page 8Linked to original sources
PubMed1979

Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients.

The peripheral interactions of amphetamine with antipsychotic agents may elucidate some central mechanisms by which these drugs affect the behavioral responses to amphetamine. The authors studied the effects of intravenous amphetamine on plasma levels of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), pulse rate, and blood pressure in schizophrenic patients. Amphetamine increased plasma NE, pulse rate, and blood pressure without significantly changing plasma DBH. DBH activity was similar in drug-free schizophrenic and normal subjects. Neither pimozide nor lithium altered these amphetamine effects nor changed any of the cardiovascular parameters measured in the drug-free subjects. Pimozide and lithium alter behavior and the behavioral effects of amphetamine, but neurotransmitters other than NE may be involved.

Adolescent↗
PubMed1979

The central noradrenergic system and affective response to MAO inhibitors.

1. In humans, norepinephrine (NE) has been postulated to be involved in the regulation of mood and behavior and to be altered in patients with manic-depressive illness. 2. Recent methodological advances have made possible a more direct assessment of central noradrenergic activity by the accurate measurement of the small amounts of NE and of the enzyme responsible for the conversion of dopamine to NE, dopamine-beta-hydroxylase (DBH), found in cerebrospinal fluid (CSF). 3. Cerebrospinal fluid samples were obtained from depressed patients both before and after treatment with two monoamine oxidase-inhibiting antidepressant drugs, clorgyline and pargyline. 4. Patients were rated twice daily by nursing staff on a modified 15-point scale for severity of global depression and anxiety. Patients were also rated using the Hamilton depression rating scale. 5. High negative correlations were observed between the drug-related changes in CSF NE and the changes in depression ratings on both the global ratings (r = -.95, p less than .001) and the Hamilton rating scale (r = -.81, p less than .01). Changes in NE were also highly correlated with changes in global anxiety ratings (r = -.85, p less than .01) calculated on the basis of changes from baseline for each measurement. Drug-related changes in CSF DBH similarly showed negative correlations with clinical response (r = -.79, r = -.38, r = -.68 respectively). In contrast, no significant correlations were found when drug-related changes in CSF MHPG were compared to changes in clinical state.

Adult↗
PubMed1979

Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress.

Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.

Animals↗
PubMed1979

Hemodynamic and plasma catecholamine responses to hyperthermic cancer therapy in humans.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.

Adult↗
PubMed1979

Relationship of sympathetic nervous system tone and blood pressure.

Plasma concentrations of norepinephrine (NE) appear to reflect sympathetic nervous system (SNS) tone. Plasma NE increases substantially when the SNS is stressed by acute postural change or physical exercise. Standing up from the recumbent position elevates NE by about 90% in healthy normotensive and hypertensive subjects. Although a primary role of the SNS is the maintenance and stabilization of blood pressure, there does not seem to be a direct relationship between plasma levels of NE and blood pressure. Patients with essential hypertension cannot be differentiated from normotensive subjects of the same mean age on the basis of either basal plasma levels of NE nor increments in NE after a standard postural stress. Patients with syndromes affecting the autonomic nervous system who suffer from orthostatic hypotension may have striking abnormalities in SNS response to stress, and some subgroups may be distinguished on the basis of the plasma concentrations of NE and the changes in NE elicited by stress.

Adolescent↗
PubMed1979

Effect of inhibition of prostaglandin synthesis on sympathetic nervous system function in man.

The effect of inhibition of prostaglandin synthesis by indomethacin on the function of the peripheral sympathetic nervous system was studied in eight normotensive subjects. Sympathetic nervous function was assessed by measurement of plasma norepinephrine, alpha-adrenergic receptor sites on platelet membranes, and urinary excretion of epinephrine and norepinephrine. Treatment with indomethacin for 7 days resulted in significant decreases in basal plasma norepinephrine from 134 +/- 7 to 99 +/- 6 (SEM) pg/ml (P less than 0.01), a 26% decrease. Posturally stimulated norepinephrine concentrations (337 +/- 14 pg/ml in control studies) were 255 +/- 18 pg/ml (P less than 0.02), 25% lower, with indomethacin. Plasma norepinephrine after 5-min compression of hand grip (468 +/- 47 pg/ml in control) was 331 +/- 30 pg/ml (P less than 0.005), 29% lower, with indomethacin. The number of platelet alpha-adrenergic receptor sites did not change with indomethacin, nor did prostaglandin E1-stimulated cAMP production by platelet membranes. In addition, indomethacin produced no change in urinary excretion of norepinephrine or epinephrine. It is suggested that inhibition of prostaglandin synthesis may lead, via baroreceptor feedback, to a decrease in plasma norepinephrine concentration.

Adult↗
PubMed1979

Catecholamine metabolism in primary anorexia nervosa.

Abnormalities in neuroendocrine function and sympathetic nervous system activity appear to be present in primary anorexia nervosa. Hypothalamic catecholamines are involved in control of endocrine function and norepinephrine is released from sympathetic nerve endings. Because of possible abnormalities in catecholamine metabolism, plasma levels of norepinephrine and urinary excretion of homovanillic acid and 3-methoxy-4-hydroxyphenyl glycol were studied in female patients with primary anorexia nervosa before and after significant clinical improvement and compared with normal female volunteers. During the phase of the disease in which body weights were more than 20--25% below ideal, patients' blood pressures and pulse rates, plasma levels of norepinephrine, and 24-h urinary excretion of 3-methoxy-4-hydroxyphenol glycol and homovanillic acid were lower than those of a group of normal volunteers. After weight gain, these parameters increased to near-normal levels. At no time was plasma dopamine-beta-hydroxylase activity abnormal. The results suggest that abnormalities in catecholamine metabolism in primary anorexia nervosa are caused by starvation, and that neuronal functions dependent on aminergic neurotransmission may be altered as a result.

Adolescent↗
PubMed1979

Adrenergic receptor function is different in male and female patients with essential hypertension.

As plasma norepinephrine (NE) levels may be similar in hypertensive and normotensive subjects, the sensitivity of adrenergic receptors was investigated in patients with essential hypertension and normotensive subjects of similar age and sex. Alpha-adrenergic receptor sensitivity was measured in platelets by the specific binding of [3H]dihydroergocryptine and the NE inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production. The number of alpha-adrenergic receptors in platelets from hypertensive women was 1.5 times that in the platelets from normotensive ones, with no differences between hypertensive and normotensive women or between men and women in the affinity of the alpha-adrenergic receptor for [3H]dihydroergocryptine. PGE1-stimulated cAMP production was half as great in hypertensive as in normotensive men, while NE inhibition of PGE1-stimulated cAMP production was similar in hypertensive and normotensive men and women. [3H]Dihydroergoeryptine binding in female hypertensives, and PGE1-stimulated cAMP in male hypertensives did not differ from that in sex-matched controls. The sensitivity of the beta-adrenergic receptor, measured by [3H]dihydroalprenolol binding and cAMP production was similar in hypertensive and normotensive subjects.

Cyclic AMP↗
PubMed1978

Plasma dopamine-beta-hydroxylase activity and norepinephrine levels during the human menstrual cycle.

Plasma samples obtained throughout the normal menstrual cycles of six women were analyzed for dopamine-beta-hydroxylase activity (DBH), norepinephrine (NE), follicle-stimulating hormone, luteinizing hormone, and prolactin. Neither DBH activity nor NE concentrations paralleled changes in plasma gonadotropins and prolactin. No consistent pattern of either plasma DBH activity or NE concentrations during the normal menstrual cycle was noted. Thus, an association between peripheral sympathetic nervous system activity and the midcycle surge in plasma gonadotropins reported by others was not reproducible in our study of normally menstruating women.

Dopamine beta-Hydroxylase↗
PubMed1978

The circadian variation of catecholamine metabolism in the subhuman primate.

Cerebrospinal fluid (CSF) was removed continuously in 2- or 3-h aliquots from the lateral and fourth cerebral ventricles of chronic chair restrained rhesus monkeys. Under conditions of 12 h light (06.00-18.00 h) and 12 h darkness (18.00-06.00 h) the concentrations of norepinephrine (NE) were found to describe a circadian pattern, with maximal concentrations occurring during the light hours and minimal concentrations occurring during the dark hours. The patterns were generally coincident with the circadian patterns of brain temperature and body activity. When assayed for 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA), samples of CSF collected over 3-4 days demonstrated no reproducible pattern of change. Fluctuation in the concentration of MHPG did not correspond in direction or magnitude to changes in the concentration of VMA. These random fluctuations may in part be accounted for by the influx of the metabolites from peripheral sources to the brain and CSF, and by the relatively slow movement of these metabolites as they diffuse from brain parenchyma to the CSF.

Animals↗
PubMed1978

Probenecid-induced norepinephrine elevations in plasma and CSF.

Probenecid administered in divided oral doses totaling 100 mg/kg increased levels of norepinephrine (NE) in plasma and cerebrospinal fluid (CSF). This technique is commonly used to measure the rate of accumulation of acidic metabolites of certain brain neurotransmitter biogenic amines in CSF after blockade of their transport into blood. Since levels of 3-methoxy-4-hydroxy-phenylethyleneglycol, a neutral metabolite of NE, are also elevated after high oral doses of probenecid, the increases of CSF and plasma NE levels may be directly related to probenecid-induced release of this amine from noradrenergic neurons. In patients who experienced nausea or vomiting there were lower levels of probenecid in CSF, probably secondary to diminished absorption of the medication. These patients also had lower levels of NE in plasma than did patients who remained asymptomatic.

Adolescent↗
PubMed1978

Response of norepinephrine and blood pressure to stress increases with age.

While at rest young subjects have lower mean arterial blood pressure than old subjects and lower circulating levels of the neurotransmitter of the sympathetic nervous system, norepinephrine (NE). After standing and performing an isometric exercise, young subjects increase their circulating levels of NE less than old subjects. The cold pressor test is commonly used as a stimulus to the sympathetic nervous system, and young subjects have a much smaller pressor response than old subjects. In response to uniform stresses young subjects secrete less NE and have a smaller blood pressure response than old subjects.

Adolescent↗