Plasma Dopamine Levels Research Articles

Plasma catecholamines in rats exposed to cold: Effects of ganglionic and adrenoreceptor blockade

Exposure to cold (4°C) of catheterized rats acclimated to 20°C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20°C) by about 30 min. No further increase in plsama NA levels were detected when the cold exposure was continued for 24 h. Plasma adrenaline (A) and dopamine levels did not change at any time studied. Adrenalectomized rats exposed to cold exhibited percent rises in plasma NA similar to those in intact rats. An increase in plasma A levels concomitant with that of NA was observed following exposure to cold of rats in which either basal catecholamine release was impaired by chlorisondamine or the vasoconstrictor response was impeded phentolamine. Propranolol did not modify the acute neurosympathetic response to cold. Exposure to cold (4°C) for short periods of time combined with the measurement of plasma catecholamines is proposed as a useful and reproducible method for studying a pure neurosympathetic response in the rat.

The role of catecholamines in the control of gastrin and acid secretion during insulin hypoglycaemia in man.

5 adrenalectomized subjects and 8 healthy volunteers underwent an insulin test during which acid secretion and plasma adrenaline, noradrenaline, dopamine and gastrin concentrations were measured. Plasma glucose concentration fell by greater than 50% in all subjects. The mean plasma adrenaline concentration increased markedly (greater than 1,000%) in the normal group but was unchanged in the adrenalectomized group. In all subjects, plasma noradrenaline concentration increased moderately, whereas plasma dopamine levels remained unchanged. Clear-cut increments in plasma gastrin concentration were seen only on 3 participants, each of whom responded to insulin hypoglycaemia with an extremely high adrenaline release. Basal and peak acid output were similar in adrenalectomized and normal subjects. The results suggest that circulating catecholamines contribute to the control of gastrin and acid secretion in man only during circumstances with high plasma catecholamine levels, e.g. severe stress.

Role of haemodynamics, catecholamines and renin in acute hypercalcaemic hypertension in man.

1. The effect of acute hypercalcaemia on blood pressure, blood volume, haemodynamic indices, plasma catecholamines, renin and aldosterone levels was investigated in 10 patients. 2. Calcium infusion (15 mg/kg over 3 h) increased (P < 0.05) plasma calcium and adrenaline levels, blood pressure, total peripheral resistance and packed cell volume. Plasma volume was decreased, and heart rate, cardiac output and plasma renin, aldosterone or dopamine levels were not significantly changed. Plasma noradrenaline was increased only minimally after 3 h of calcium infusion. 3. Mean blood pressure before and during calcium infusion correlated with concomitant serum calcium (r = 0.39; P < 0.02) or adrenaline levels (r = 0.57; P < 0.01); changes in blood pressure correlated with variations in plasma adrenaline (r = 0.68; P < 0.001). 4. Acute hypercalcaemic hypertension is mediated by an increase in peripheral vascular resistance and may be induced by a direct effect of calcium on blood vessels. The calcium-mediated increase in adrenaline release may play a contributory, and plasma volume contraction an inhibitory, role.

Abnormal sympatho-adrenal function and plasma catecholamines in obese Zucker rats

The functional integrity of the peripheral sympathetic nervous system and adrenal medulla was assessed in homozygous, lean and obese, 7–8 month old male Zucker rats by the changes in plasma catecholamines during cold and immobilization stresses. Five of eight obese, but no lean rats died during a 24 hr cold stress (4–7°C) from hypothermia. While both lean and obese rats had decreased rectal temperatures after 4 hr of cold stress, the obese had lower temperatures, relatively less of an increase of plasma norepinephrine (NE) and epinephrine (E) than the lean rats, and were unable to consistently maintain their temperatures even during intravenous NE infusions. Obese rats had lower rectal temperatures and higher plasma NE and dopamine levels at 21–22°C ambient temperature, a relative failure to increase plasma NE and E levels after 1 hr of immobilization, but normal or supranormal plasma catecholamine levels after decapitation compared to the lean rats. These results suggest that the obese Zucker rat has abnormalities of both peripheral sympatho-adrenal function and thermoregulation, which may play roles in the development and/or maintenance of many of the physiological and metabolic defects in this animal model of genetic obesity.

Renin-hyporesponsiveness in essential hypertension. Dissociation between plasma renin and catecholamines or aldosterone following furosemide.

The influences of sequential stimulation with upright posture and sodium depletion by intravenous furosemide on blood levels of norepinephrine, epinephrine, dopamine, renin and aldosterone was studied in 26 normal subjects and 45 patients with borderline (N=20) or established (N=25) essential hypertension. Basal 24-h urinary sodium, norepinephrine and epinephrine excretion rates and basal (supine) plasma catecholamine, renin and aldosterone levels and the body sodium-volume state were comparable between the three groups. Assumption of the upright posture for 10 to 60 min caused significant increases in plasma norepinephrine (P<0.001), epinephrine (P<0.001) or dopamine (P<0.05) levels. Upright plasma catecholamine concentrations were similar in normal and hypertensive subjects and they were not modified further by furosemide. In contrast upright posture as well as furosemide induced each a successive significant (P<0.02) increase in plasma renin and aldosterone levels. Furosemide-stimulated renin was significantly (P<0.05) lower in patients with established hypertension than in normal or borderline hypertensive subjects; however, plasma aldosterone levels were comparable. These findings suggest that renin release induced by furosemide is not mediated by increased adrenergic activity. Consequently, renin-hyporesponsiveness in established hypertension cannot be explained by decreased sympathetic activity. In contrast to the altered renin regulation, aldosterone-responsiveness to upright posture or furosemide as well as adrenergic activity under these conditions appear to be usually normal in borderline or established hypertension.

Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus

Diabetes mellitus is often associated with excess body sodium and frequently accompanied by hypertension. Relationships among blood pressure and various regulatory factors were studied before and after six weeks of diuretic therapy with chlorthalidone, 100 mg/day, in 17 diabetic subjects (aged 32 to 75 years) with borderline to moderate hypertension. Following a four-week placebo phase, mean supine blood pressure was 165/93 ± 26/15 (±SD) mm Hg and exchangeable sodium was increased (49 ± 4 versus 45 ± 4 meq/kg lean body mass in 90 normal subjects; p < 0.01). Blood volume, and supine and upright plasma renin, aldosterone, norepinephrine, epinephrine or dopamine levels were comparable to normal values. Measurements in eight diabetic subjects revealed an increased cardiovascular reactivity, as evidenced by decreased (p < 0.001) pressor doses of norepinephrine (68 ± 42 versus 151 ± 52 ng/kg/min) or angiotensin II (3.9 ± 1.2 versus 10.3 ± 5.5 ng/kg/min). Chlorthalidone decreased blood volume by 11 per cent, lowered body sodium (by 9 per cent) and cardiovascular sensitivity to norepinephrine (by 48 per cent) or angiotensin II (by 60 per cent) towards normal and reduced blood pressure by 11 per cent to 145/82 ± 13/12 mm Hg (11 per cent). Plasma renin and aldosterone were markedly increased by chlorthalidone, whereas plasma and urinary catecholamine levels were not significantly altered. These findings suggest that hypertension in patients with diabetes mellitus may partly depend on increased body sodium and/or an exaggerated cardiovascular reactivity to norepinephrine and angiotensin II. The blood pressure-lowering effect of diuretic therapy may be due to removal of excess sodium and the restoration of norepinephrine pressor sensitivity towards normal without an equivalent increase in adrenergic nervous activity.

Effect of histamine and acetylcholine on hypophysial stalk plasma dopamine and peripheral plasma prolactin levels

To further define the role of dopamine in the regulation of prolactin secretion, we studied the effect on prolactin and hypothalamic dopamine secretion of histamine and acetylcholine (ACh) injected into the lateral ventricle of urethane anesthetized diestrus-1 rats. Histamine (10 μg) caused a 592% increase in plasma prolactin levels and a 26% decrease in stalk plasma dopamine levels. ACh (50 μg) caused a 2090% increase in plasma prolactin levels but no significant change in stalk plasma dopamine concentration. To determine if the 26% fall in stalk plasma dopamine following histamine administration could account for the 6-fold increase in plasma prolactin, we measured the effect on prolactin secretion of a similar decrease in administered dopamine. During an infusion of physiologic levels of dopamine, a 25% decrease in arterial plasma dopamine concentration resulted in only a 2-fold increase in prolactin secretion. The results of these experiments suggest that the effect of histamine on prolactin secretion may be mediated in part by decreased hypothalamic secretion of dopamine but that an additional hypothalamic hormone is probably involved. The stimulatory effect of ACh on prolactin secretion is not mediated by dopamine. These data are consistent with the growing evidence for the participation of multiple hypothalamic factors in the regulation of prolactin secretion.

Effects of electric stress on glucose metabolism, glucose-stimulated cyclic adenosine 3',5'-monophosphate accumulation and 45Ca++ efflux in isolated pancreatic islets from rats fed with a high fat diet.

The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and 45Ca++ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks. The half of rats on each diet were subjected to electrical shocks in the random time schedule for 1 hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20 min of incubation with 2.8 mM glucose was decreased in islets from F-S group without affecting insulin release. After 20 min of incubation with 25 mM glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7 mM)-stimulated 45Ca++ efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7 mM glucose was decreased in islets from F-S group. It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets.

Dopamine levels in hypophysial stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo.

Much evidence indicates that dopamine can inhibit PRL secretion. However, it is still unclear whether dopamine acts on hypothalamic neurons to stimulate PRL-inhibiting factor (PIF) release or whether dopamine is itself PIF, acting directly on the pituitary. This study was designed to determine if PRL secretion is inhibited by dopamine infusions producing plasma dopamine levels which mimic those found in hypophysial stalk plasma. Stalk plasma dopamine concentration in urethane-anesthetized diestrus-1 rats was 6.0 ± 1.1 ng/ml (mean ± SE; n = 10). During a dopamine infusion, stalk plasma dopamine levels were 70% of arterial levels. Therefore, dopamine was infused at a rate which achieved arterial levels of 9–10 ng/ml and the effect on PRL secretion in urethane-anesthetized female rats was measured. In diestrus rats, dopamine did not inhibit PRL secretion. In rats pretreated with α-methyl-p-tyrosine to elevate serum PRL levels, dopamine suppressed PRL secretion 70%. In rats with PRL levels elevated by median ...

Dopamine in hypophysial portal plasma of the rat during the estrous cycle and throughout pregnancy.

Catecholamine levels in hypophysial portal plasma were determined in pregnant and non-pregnant female rats as well as in intact and castrated male rats, using a radioenzymatic assay for the simultaneous determination of dopamine, norepinephrine, and epinephrine in 50 mul of plasma. Portal and arterial blood were collected from anesthetized rats at 7 mul/min for 60 min. During the collection, blood was kept at 0 C, a temperature at which endogenous catecholamines were relatively stable. Dopamine was present in high concentrations in hypophysial portal plasma thorughout pregnancy, attaining a level near 20 ng/ml on the 20th day of gestation. Dopamine levels in arterial plasma from the same rats were low or undetectable (0.4--0.8 ng/ml1. Norepinephrine and epinephrine was undetectable (less than 0.6 ng/ml) in portal as well as arterial plasma from these rats. The major catecholamine in extracts of the hypothalamus from pregnant rats was norepinephrine, whereas that in the posterior pituitary was dopamine. Dopamine levels in portal plasma collected during proestrus, estrus, diestrus 1, and diestrus 2, were 1.32 +/- 0.21 (mean +/- SE), 3.87 +/- 0.96, 3.11 +/- 0.73, and 2.3 +/- 0.45, respectively. Dopamine in portal plasma from intact and from castrated male rats was approximately 0.6 ng/ml. Norepinephrine and epinephrine were not detectable in either portal or arterial plasma from these animals. It is concluded 1) that dopamine is secreted into hypophysial portal blood in significant quantities during pregnancy, 2) that hypothalamic secretion of dopamine in cyclic rats is greatest during the day of estrus and early diestrus and at least on the day of proestrus, and 3) that these findings support the view that dopamine of hypothalamic origin may have an important role in the regulation of anterior pituitary function.

Assay of catecholamines in human plasma: Studies of a single isotope radioenzymatic procedure

The sensitive specific radioenzymatic procedure for determination of catecholamines originally described from our laboratory by Coyle and Henry (1) has been optimized for use in assay of human plasma levels of dopamine, norepinephrine and epinephrine. Dopamine and the total of norepinephrine and epinephrine are assayed by 0-methylation while norepinephrine is determined by N-methylation. Epinephrine is calculated from the difference between the 0-methylation and N-methylation procedures. In a group of 13 normal subjects, plasma levels of epinephrine were found to be 67 ± 9.2 pg/ml, norepinephrine 208 ± 16.9 pg/ml and dopamine 33 ± 8.1 pg/ml. Dopamine determinations are of low reliability because of relatively high blanks and necessary corrections.

Dopamine: A sensitive automated assay and examples of levodopa therapy

The fluorometric determination of dopamine by oxidation with potassium ferricyanide in an alkaline medium was automated using the Technicon AutoAnalyzer. The method is rapid, sensitive, and reproducible. The concentration of dopamine in whole rat brain determined by this method was 5.15 nmole/g, agreeing closely with values in the literature. Plasma levels of dopamine and dopa were determined at half-hour intervals in patients receiving levodopa therapy. Dopa and dopamine concentrations in plasma rose and fell in response to each dosage, but patients show considerable individual variations in their pattern of plasma levels. In the presence of carbidopa, a peripheral dopa decarboxylase inhibitor, dopamine concentrations could not be detected.

L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism.

Eighteen patients with parkinsonism were treated with a combination of L-dopa and peripheral decarboxylase inhibitor, L-alphahydrazinomethyldopa (MK-486). Modification of L-dopa effect by MK-486 was also studied in parkinsonian patients as well as in cats. (1) Concentrations of dopa and dopamine in plasma and brain were measured in cats following intraperitoneal injection of L-dopa alone (100 mg/kg) or combined with MK-486 (10 mg/kg). Dopa levels in plasma and brain in the combination with MK-486 were three times as high as in L-dopa alone. Dopamine levels in caudate nucleus and putamen were increased nearly fourfold with the combination. (2) Plasma dopa and dopamine levels were measured in parkinsonian patients. Clinical pharmacological studies disclosed that a 1 : 10 ratio of MK-486 to L-dopa in dosage was preferable. (3) Maximum plasma dopa levels with the combination were four times those following L-dopa alone. Plasma dopa sustained a high level over a period of five hours. MK-486 markedly reduced plasma levels of dopamine. (4) There was no significant difference in dopa and dopamine levels in cerebrospinal fluid between L-dopa alone and a combination of MK-486, but dopamine levels in the CSF were still high at four hours after the combination of MK-486. (5) In clinical studies of eighteen patients with parkinsonism, the effectiveness of the combination therapy (mean dosage of L-dopa: 750 mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 15 (67%) with akinesia, in 12 cases out of 17 (71%) with rigidity and in six cases out of 14 (43%) with tremor. Maximum plasma dopa levels were higher in those cases with marked improvement, and were highest in patients with diskinesias as a side effect. (6) An addition of vitamin B6 did not show adverse effects. (7) Transient nausea and vomiting as a side effect, less severe than those experienced with L-dopa alone, were noted in five cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in six cases (33%). These dyskinesias were seen in a high percentage of cases with marked improvement and were never observed in the extremities contralateral to the side of thalamotomy.

カテコールアミン代謝に関する基礎的ならびに臨床的研究

Combined effects by L-DOPA and peripheral decarboxylase inhibitor (L-alpha-hydrazinomethyldopa: MK 486) were studied in cats and eighteen parkinsonian patients, with special reference to catecholamines and amino acids metabolism.Catecholamine levels in brain tissues and plasma were measured in cats following the intraperitoneal injection of L-DOPA alone (100mg/kg b. w.) or combined with MK 486 (10mg/kg b. w.) by gas chromatographic method (using an Electron Capture Detector).1) DOPA level in cat plasma in the combination with MK 486 was three-fold as high as in L-DOPA alone. Dopamine levels in caudate nucleus of cats were increased up to about six-fold in the combination. Dopamine level in plasma was markedly decreased in the combination with MK 486. Norepinephrine and epinephrine levels in cat plasma were no significant change in both L-DOPA alone and combination with MK 486. Norepinephrine level in the brain was no significant change except slight increase in pallidum and caudate nucleus.2) After oral administration of L-DOPA in combination with MK 486, DOPA level in plasma of the patients with parkinsonism was maintained at a higher level and for longer than after the oral administration of L-DOPA alone. Plasma dopamine level with the combination was markedly lower than with L-DOPA alone. Dopamine level in plasma at three hours after the administration tended to be decreased at a 1:5 ratio of MK 486 to L-DOPA in dosage. Plasma epinephrine level was not significant change at all. Dopamine level in cerebrospinal fluid was maintained at a higher level and for longer than the oral administration of L-DOPA alone.3) Urinary homovanillic acid level in parkinsonism was lower in the combination of MK 486.4) Plasma amino acids which might affect catecholamines metabolism was not significant change following the administration of L-DOPA alone as well as L-DOPA plus MK 486.5) In clinical studies of 18 patients with parkinsonism, the effectiveness of the combination therapy with L-DOPA and MK 486 (mean dosage of L-DOPA: 750mg/day and MK 486: 75mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 18 (56%) with akinesia, in 12 cases out of 18 (67%) with rigidity and in 6 cases out of 18 (33%) with tremor. Maximum plasma DOPA levels were higher in cases with marked improvement than the other, and were highest in patients with dyskinesias of a side effect.6) Nausea and vomiting of the side effect, which were less severe than those experienced with L-DOPA alone, were noted in 5 cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in 6 cases (33%).

Studies on the Combined Effect by L-DOPA and L-alpha-hydrazinomethyldopa (MK 486) in Parkinsonism, with a Special Reference to Catecholamine Metabolism

Following oral administration of L-DOPA alone or L-DOPA in combination with extracerebral DOPA decarboxylas inhibitor (L-alpha-hydrazinomythyldopa: MK 486), catecholamines level in plasma and cerebrospinal fluid of patients with Parkinsonism were determined by gaschromatography (ECD).After oral administration of L-DOPA in combination with MK 486, DOPA level in plasma was maintained at a higher level and for longer than after the oral administration of L-DOPA alone. Dopamine level in plasma was markedly lower than with L-DOPA aloneDopamine level in cerebrospinal fluid after oral administration of L-DOPA in combination with MK 486 was maintained at a higher level than after the oral administration of L-DOPA alone.Thus, judging from DOPA and dopamine levels in plasma, a combination-ratio of L-DOPA and MK 486 of 10 to 1 was found to be desirable.

Dopamine generated from L-dopa: discrepancy between plasma levels and cardiac effects.

SummaryEvidence has been presented in anesthetized dogs indicating that dopamine generated from l-dopa is predominantly in a pharmacologically inactive form whose identification is presently unknown, but there is some suggestion that it may be a labile conjugated derivative. The discrepancy between the high dopamine plasma levels after intravenous l-dopa administrations with the low cardiac contractile force responses were disclosed by comparison with the correlations obtained following dopamine infusions.