Dopamine-beta-hydroxylase Levels Research Articles

Contribution of adrenal medulla, spleen and lymph, to the plasma levels of dopamine beta-hydroxylase and catecholamines induced by hemorrhagic hypotension in dogs.

Contribution of adrenal medulla, spleen and lymph, to the plasma levels of dopamine beta-hydroxylase and catecholamines induced by hemorrhagic hypotension in dogs.

Dopamine-β-hydroxylase and norepinephrine in human cerebrospinal fluid: Effects of monoamine oxidase inhibitors

The effect of the monoamine oxidase inhibitors, clorgyline and pargyline, on central noradrenergic function in depressed patients was assessed by measuring dopamine beta hydroxylase (DBH) and norepinephrine in cerebrospinal fluid (CSF). These drugs caused a significant decrease in DBH in CSF. This decrease is consistent with a reduction in the release of DBH into CSF as noradrenergic firing is slowed by the drugs. Levels of DBH and norepinephrine in CSF were highly correlated. The ratio of CSF norepinephrine to CSF DBH increased when the patients were treated with monoamine oxidase inhibitors, consistent with a drug-induced increase in brain norepinephrine.

Dopamine-beta-hydroxylase activity and catecholamine levels in the plasma of patients with renal failure.

In 25 patients with end-stage renal failure and 9 patients treated with hemodialysis an increase in norepinephrine (NE) and epinephrine (E) concentrations in the plasma and a decrease in the dopamine-beta-hydroxylase (DBH) activity was ascertained. DBH, NE and E concentrations were determined in some patients before and after commencement of the chronic hemodialysis program. NE concentration increased further both before and after single hemodialysis comparing to previous levels, E increased only after single dialysis but DBH levels did not change. NE concentration in the blood showed a positive correlation with DBH activity in healthy persons and hemodialysed patients. The observed increase in the catecholamine concentrations and decrease in the DBH activity is an evidence of dysfunction in the autonomic nervous system.

Low serum dopamine beta-hydroxylase activity. A marker of congestive heart failure.

To gain information about the nature of disturbances in sympathetic nervous system control in congestive heart failure, serum dopamine beta-hydroxylase (DBH) activity was measured in 30 patients with heart failure of diverse etiologies and 29 healthy normotensive controls. The heart failure patients had been symptomatic for at least 6 wk and had elevated filling pressures, low cardiac indices, low ejection fractions, and wide arteriovenous oxygen differences. DBH activity was 47.1+/-4.7 (mean+/-SE) for the controls and 14.4+/-2.7 IU for the heart failure patients (P < 0.001). Sera from some patients with heart failure had potent inhibitory effects on DBH activity of normal sera. The inhibitor was heat stable and dialyzable and could be demonstrated despite presence of N-ethylmaleimide or Cu(++) in the reaction mixture. However, some inhibitory activity was also present in sera of normal patients; this inhibitory property was not demonstrable in unheated normal serum, but was unmasked when DBH was heat inactivated. It is proposed that although the inhibitor may have been a factor in low serum DBH activity in some patients with heart failure, the major cause of the low activity in the heart failure group was a reduced rate of synthesis or release of the enzyme by sympathetic nerves. This may reflect a dissociation between rates of neural release of norepinephrine and release of DBH in chronic, severe heart failure. The observation of low serum DBH levels in patients with heart failure suggests that measurement of DBH levels may serve as a useful indicator of cardiac dysfunction.

Changes in plasma dopamine beta-hydroxylase activity induced by stimulation of the complete sympathetic outflow in the pithed rat.

1. Plasma dopamine beta-hydroxylase (DBH) activity, noradrenaline tissue levels and blood pressure were monitored in the pithed rat following electrical stimulation of the complete sympathetic outflow of the spinal cord. Stimulation at 10 or 30 Hz evoked marked increases in mean blood pressure which averaged 121 mmHg and were abolished by phenoxybenzamine. 2. Stimulation for 1 hr at 10 or 30 Hz did not change the noradrenaline content of the spleen nor the catecholamine content of the adrenals, but the heart noradrenaline content was doubled. 3. Plasma DBH activity was increased by 27% after 1 hr stimulation at 30 Hz, but remained unchanged after stimulation at 10 Hz, or at 30 Hz in phenoxybenzamine-treated rats. 4. We conclude that the pressor responses evoked by sympathetic nerve stimulation are due to the release of noradrenaline probably from adrenergic nerve terminals supplying the entire vasculature, and that acute alterations of circulating DBH activity are not dependent on the rate of catecholamine release evoked by direct electrical stimulation of sympathetic nerves in the whole pithed rat. The rat seems not to be a good model to study circulating noradrenaline and DBH levels as an index of exocytotic noradrenaline release from adrenergic neurones, and therefore of sympathetic activity.

Effect of acute volume alterations on norepinephrine and dopamine-beta-hydroxylase in normotensive and hypertensive subjects.

Fifty-six patients with essential hypertension and 29 normotensive controls were hospitalized and volume expanded with saline or volume depleted with furosemide. We measured plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) to evaluate their sympathetic nervous activity. NE and DBH levels and their response to volume changes were the same in normal and hypertensive subjects. Volume depletion increased plasma NE in recumbent subjects by 50% and in standing subjects by 75% but did not alter DBH. Volume expansion with 2 liters of normal saline did not generally alter plasma NE, but led to a small decrease in DBH. Hypertensives have normal plasma levels of NE and DBH and normal responses of NE and DBH to alterations in volume and posture. The human sympathetic nervous system increases NE output during volume depletion, but fails to decrease NE during volume expansion.

Effect of acute blood volume expansion on cardiac output, plasma dopamine beta-hydroxylase, and renal function in rats with chronic constriction of the ascending aorta.

To examine the effect of raised left atrial pressure (AP) on the relationship of cardiac output to renal function, we constricted the ascending aorta in rats (AC) and 1-6 months later tested their response to acute volume expansion (VE) with blood (2% body weight, iv). Sham-operated (SH) rats were controls. In AC rats heart weight increased 38%, but cardiac output was 47% lower. Statistically significant differences in the initial clearance periods were (AC vs. SH): venous pressure (VP) 8 +/- 2 vs. 3+/- 1 cm H2O; inulin clearance (CIN) 0.61 +/- 0.06 vs. 0.84 +/- 0.04 ml/min; sodium excretion (UNAV) 1.2 +/- 0.2 vs. 2.1 +/- 0.3 muequiv./min. Filtration fraction, fractional UNaV, mean arterial pressure (MAP), and plasma dopamine beta-hydroxylase (DBH) were the same in both groups. After VE, cardiac output increased proportionately more in AC (69% vs. 27%); however, the absolute increases were not different. UNaV increased proportionately more in AC rats, but the absolute increase was less (5.1 vs. 7.5 muequiv./min). Multiple variable regression analysis showed that UNaV correlated with CIN, MAP, and VP, with no difference between AC and SH animals. Cardiovascular-renal relationships were indistinguishable from previous descriptions of dogs and rats with chronic vena caval constriction. Modulation of renal function by left AP was not apparent. In both groups after the peak response to VE, UNaV decreased in association with decreased cardiac output and increased sympathetic nervous activity as indicated by raised DBH levels. After VE, VP remained high in AC but not in SH animals.

Can Dopamine Beta‐Hydroxylase Levels Predict Adverse Reactions to Disulfiram?

Disulfiram had more pronounced sedative effects on healthy normal subjects with low levels of plasma dopamine-beta-hydroxylase (DBH) than it did on subjects with higher levels. It is suggested that DBH levels might provide a means of predicting increased susceptibility to disulfiram side effects.

Absence of a relationship between sympathetic neuronal activity and turnover of serum dopamine-beta-hydroxylase.

The effects of pharmacological alteration of adrenergic transmission on the rate of entrance of dopamine-beta-hydroxylase (DBH) into the circulation were assessed in rats by an immunological method in which the kinetics of recovery of serum DBH activity were measured after depletion of the enzyme by treatment with anti-rat DBH antiserum. Neither alpha-receptor blockade with phenoxybenzamine nor ganglionic blockade with clorisondamine altered the rate by which DBH enters the bloodstream although both treatments markedly altered serum catecholamine levels. Prolonged treatment of newborn rats with guanethidine produced a severe peripheral sympathectomy but only a moderate decrease (30%) in serum DBH levels. In the sympathectomized rats, the rate of entrance of DBH into the circulation was significantly reduced whereas the half-life and rate of degradation of the enzyme was unchanged. These results indicate that the major portion of serum DBH does not enter the circulation by means of exocytotic release of the soluble enzyme.

Systemic hypertension associated with coronary artery bypass surgery: Predisposing factors, hemodynamic characteristics, humoral profile, and treatment

Systemic hypertension occurs in more than one third of patients having coronary artery bypass graft (CABG) operations. This report describes our studies in 100 consecutive patients undergoing CABG. We found that certain preoperative clinical, angiographic, and biochemical factors predispose to the development of perioperative hypertension. These included a well-documented history of hypertension, an elevated blood pressure the day prior to operation, greater than 50 percent obstruction of the left main coronary artery, and increased levels of dopamine beta hydroxylase (DBH). The hemodynamic pattern of perioperative hypertension was that of an increased systemic vascular resistance which was associated with increased levels of plasma catecholamines and plasma renin activity (PRA). Nitroprusside was shown to be effective in managing CABG hypertension, although other, more specific therapy may be preferable.

Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.

Enhanced sympathetic activity in young spontaneously hypertensive rats is not the trigger mechanism for genetic hypertension.

In young, spontaneously hypertensive rats (SHR), a preganglionic, nerve-dependent, elevation of choline acetyltransferase (ChAc) and tyrosine hydroxylase (TH) activities was found in celiac ganglia as compared with those in young, normotensive Kyoto Wistar rats, that was not present in superior cervical ganglia, stellate ganglia and adrenal glands. The rise in both enzyme activities in the celiac ganglion disappeared in adult SHR. An elevation of plasma norepinephrine and dopamine beta-hydroxylase levels found in prehypertensive SHR, a probable indication of peripheral sympathetic activation, disappeared after the bilateral removal of the celiac ganglion. However, ganglionectomy did not change the subsequent development of hypertension. These results indicate that the faster maturation of the celiac ganglion and the end organs it innervates in yount SHR are causally related to the activation of the peripheral sympathetic nervous system. The peripheral sympathetic activation in young SHR is regarded as a warning sign but this does not trigger the development of hypertension.

Plasma noradrenalin and dopamine-beta-hydroxylase during behavioral testine of sexually deviant XYY and XXY males.

In a behavior study of a sexually deviant XYY and XXY male, who were both murderers, plasma noradrenaline (NAA), dopamine-beta-hydroxylase (DBH) were determined radioenzymatically under resting conditions and during exertional and emotional stress. Under a physical sork load on the bicycle ergometer both had normal plasma NA and DBH levels. During emotional stress both had NA increases of the same magnitude. During an arithmetic test NA values did not increase more than expected for the sitting position.

Changes in tyrosine hydroxylase and dopamine-β-hydroxylase activities during degeneration of noradrenergic axons produced by antibodies to dopamine-β-hydroxylase

Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities were measured in various tissues of guinea-pigs 1-21 days after intravenous injection of antiserum against DBH. At 5 days a significant reduction in tissue levels of DBH was observed in all tissues measured although the extent of depletion was variable. TH in the heart and vas deferens showed a parallel reduction to DBH. At 21 days tissue DBH and TH had partially recovered. Plasma DBH was reduced at 21 days whereas adrenal TH was markedly elevated. These findings support the morphological evidence that antibodies against DBH produce a specific degeneration of peripheral noradrenergic nerves.

Serum dopamine-beta-hydroxylase activity in the affective psychoses and schizophrenia. Decreased activity in unipolar psychotically depressed patients.

Serum dopamine-beta-hydroxylase (DBH) activity was studied in 125 psychiatric patients and 73 normal controls. Serum DBH activity in schizophrenic, bipolar manic, and neurotic depressive patients was not significantly different from that in controls. Although serum DBH activity in unipolar and bipolar depressed patients was also not significantly different from that in controls, the subgroup of psychotically depressed unipolar patients had significantly lower serum DBH levels than controls did. Serum DBH activity in bipolar psychotically depressed patients also tended to be low, but was not significantly less than in controls. Serum DBH activity in the patient group usually did not increase in the immediate period following successful treatment with drugs or electroconvulsive therapy, indicating that basal levels of serum DBH activity in psychiatric patients are not state-dependent. Low serum DBH levels in psychotically depressed patients must be verified in an independent group of patients before its significance can be appreciated. Our findings could be the result of the study of an atypical group of psychotically depressed patients.

Developmental variations of tyrosine hydroxylase and acetylcholinesterase in embryonic and post-hatching chicken sympathetic ganglia

The developmental variations of tyrosine hydroxylase (TH) and of acetylcholinesterase (AChE) were studied in embryonic and post-hatching chicken sympathetic ganglia. Different levels of TH activity were found in two different flocks of White Leghorn chicken, which are probably dependent on genetic differences. These enzymatic differences, however, do not become apparent before hatching and may indicate a combined effect of genetic variation and functional demands. During the period of incubation, TH activity is characterized by a pronounced and steady increase from the twelfth day of incubation up to day 2 after hatching. This corresponds to a period of intense maturation of the sympathetic neuron. In the period following hatching, the 'fourth day fall phenomenon' previously described by us for DOPA decarboxylase (DDC), dopamine-beta-hydroxylase (DBH), and monoamine oxidase (MAO) is not seen in the TH curve. Instead, TH activity tends to remain constant between days 2 and 14 after hatching (ah). Both ganglionic protein and weight remain constant in this period, indicating a phase of general pause in protein synthesis. AChE activity increases steadily from the eighth until the twenty-first day of incubation. A sudden and significant drop in AChE activity was found at day 2 ah followed by a period of rapid increase at day 3 ah and a levelling of activity up to day 30 ah. Comparing the present variations to those observed in our previous studies on DBH, a temporal relationship between TH and DBH activity is observed during the phases of synaptogenesis and maturation but not during the phase of intense functional activity. Our results strongly suggest that before hatching in chick embryo sympathetic ganglia, the cholinergic presynaptic terminals play a role in regulating the development of the adrenergic neurons. In the period following hatching, however, the DBH and TH levels in cell bodies seem to be principally regulated by the functional activity. This results in depletion of DBH, but not TH, through liberation along with the neurotransmitter at the periphery. Depletion of DBH at the terminals may result in increased transport and thereby depletion in the cell body. This mechanism is probably responsible for the difference in the profiles of activity of DBH and TH in the cell bodies observed in the first week after hatching.

Effects of chronic nicotine administration on the denervated rat adrenal medulla.

1 The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. 2 Catecholamine depletion was obtained in the intact glands from 1-7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. 3 Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]-adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1-7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. 4 Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. 5 Dopamine beta-hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). 6 These studies suggest that although long-term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug.

Regulation of dopamine beta-hydroxylase in rat adrenal glands.

Rat adrenal gland levels of dopamine beta-hydroxylase are subject to dual control. Activation of the splanchnic nerves to the adrenal medulla by reserpine induces the synthesis of dopamine beta-hydroxylase without altering the rate of enzyme degradation. In contrast, hypophysectomy causes a decline in steady state dopamine beta-hydroxylase levels by first accelerating the rate of degradation, then by slowing the rate of enzyme synthesis as well. Adrenocorticotropic hormone administration partially reversed the effect of hypophysectomy on dopamin beta-hydroxylase degradation. These findings suggest that the trans-synaptic factors controlling dopamine beta-hydroxylase induction act by a different mechanism (enzyme synthesis) than the hormonal controls regulating steady state levels (enzyme degradation). Thus, active inhibition of enzyme degradation may be an important control in maintenance of steady state enzyme levels.

Effect of Hypophysectomy on Serum Dopamine—Beta—Hydroxylase Activity in Rat

After hypophysectomy, rat serum dopamine—beta—hydroxylase (DBH) activity rose continuously and doubled within 5 weeks. The increase in DBH levels was not reversed by replacement doses of ACTH. Vasopressin reduced the increased levels of serum DBH activity in hypophysectomized rats to those found in sham—operated control animals, but had no effect on serum enzyme activity in sham—operated controls. Three days after the last vasopressin injection, serum DBH activity in hypophysectomized animals again reached pretreatment levels. Intravascular volume seems to be a major factor in controlling serum DBH activity. It appears that the reduced intravascular volume and subsequent sympathetic neuronal hyperactivity resulting from the diabetes insipidus induced by hypophysectomy accounts for the elevated levels of serum DBH. (Endocrinology 92: 1543, 1973)

Serum dopamine-beta-hydroxylase during development of immobilization-induced hypertension.

Serum dopamine—beta—hydroxylase (DBH) activity, which appears to reflect peripheral sympathetic nerve function, was measured in rats subjected to immobilization for two hours daily over a period of four weeks. Both serum DBH and blood pressure levels increased significantly after 2 weeks of repeated immobilization. The difference in blood pressure levels between control and experimental animals remained the same under anesthesia. After 4 weeks of immobilization, there was a further increase in both serum DBH and blood pressure levels. Upon cessation of immobilization intervals, serum DBH returned to normal within five days but blood pressure remained elevated for 2 additional weeks before returning to normal. (Endocrinology 92: 953, 1973)