Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

DeQuattro, Vincent; Sjoerdsma, Albert

doi:10.1172/jci105920

Cited by 56 publications

(24 citation statements)

References 29 publications

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“…The urinary excretion of catecholamines used as a measure of overall sympathetic activity (DeQuattro & Sjoerdsma, 1968) showed no consistent pattern of change and no correlation with the effect on pressure. There were large variations in individual results when measured in the pretrial and placebo phases, and on active treatment approximately equal numbers showed increases and decreases.…”

Section: Discussionmentioning

confidence: 96%

Acebutolol in hypertension‐double‐blind trial against placebo.

Martin¹,

Phillips²,

Smith³

1978

Brit J Clinical Pharma

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1. Eleven hypertensive patients were studied in a double‐blind comparison of acebutolol, a beta‐adrenoceptor blocker, and placebo. 2. Optimum dosage defined in an open assessment varied from 200–600 mg twice daily. 3. Blood pressure and pulse rate fell significantly while patients were lying, standing and after exercise. 4. Blood pressure remained as well controlled on each patient's optimum daily dose when taken once daily, and assessed 24 h post dose. 5. There was no correlation between blood pressure reduction and changes in heart rate. On once daily therapy while blood pressure remained unchanged at 24 h post dose there was a signficant reduction in beta‐adrenoceptor blockade as measured by percentage reduction in exercise tachycardia. 6. There was no significant change in urinary catecholamine excretion or echocardiographically estimated cardiac output. 7. A correlation was found between the change in plasma renin activity (log transformed) and blood pressure reduction.

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Section: Discussionmentioning

confidence: 96%

Acebutolol in hypertension‐double‐blind trial against placebo.

Martin¹,

Phillips²,

Smith³

1978

Brit J Clinical Pharma

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“…The validity of labeled NE as a tracer for studies of NE metabolism, though amply confirmed in animal experiments and in correlative studies by Chidsey of heart muscle and urine came under scrutiny after observation of appreciably faster catecholamine metabolite turnover rates following administration of DOPA-3H to human subjects (41). This was puzzling since the data from Goodall's dopamine-j4C experiments (42) are in agreement with the turnover rates observed in this investigation as well as the studies of Chidsey and Braunwald (18).…”

Section: Discussionmentioning

confidence: 99%

“…This was puzzling since the data from Goodall's dopamine-j4C experiments (42) are in agreement with the turnover rates observed in this investigation as well as the studies of Chidsey and Braunwald (18). A difference in the distribution (43,44) and assay techniques, using a label which could enter catabolic pathways other than those stemming from NE, could account for the lower Ti (41,45). It seems more probable that the inability to administer a dose of radioisotope sufficient to measure catecholamine metabolites after a time interval long enough for equilibration of the label, made appreciation of the definitive exponent difficult.…”

Section: Discussionmentioning

confidence: 99%

Human norepinephrine metabolism

Gitlow¹,

Mendlowitz²,

Bertani³

et al. 1971

J. Clin. Invest.

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A B S T R A C T It has become increasingly apparent that evaluation of human norepinephrine metabolism simply by assay of catecholamines in urine is inadequate for differentiation of many physiological or pathological states. In an attempt to examine norepinepherine metabolism in the human subject, tritium-labeled dl-norepinephrine was administered to 11 normal adults and the definitive turnover rates and relative specific activities of norepinephrine and its major catabolites, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and normetanephrine, as well as the cumulative 24 hr isotope excretion were determined. The major endogenous norepinephrine catabolites were also quantitatively assayed. In order to verify the reliability of the isotope label, parallel studies were carried out in two patients to whom norepinephrine--"C was administered. Metabolic studies were repeated after the administration of reserpine to gain further insight into the distribution of the label.All studies demonstrated a consistent difference between the relative specific activities of the amines and their deaminated congeners, thereby indicating an uneven distribution of the labeled material. The marked decrease in the relative specific activities of the deaminated catabolites after the administration of reserpine showed that the present experimental technique succeeded in labeling, though to a limited extent, the storage or reserpine-releasable pool. A dose of reserpine known to interfere with sympathetic activity but failing to elicit a change in excretion of endogenous catecholamine catabolites, nonetheless resulted in a marked abnormality in the metabolic handling of labeled norepinephrine. It is anticipated that such studies may not only be of value in measuring sympathetic activity in the intact human

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“…AMPT blocks the biosynthesis of cate cholamines by inhibiting the hydroxylation of tyrosine to /.-dopa [DeQuattro and Sjoerdsma, 1968;Sjoerdsmaetal.. 1965]. Inhibition of this first and rate limiting step of catecholamine synthesis results in a significant reduction of endogenous levels of catecholamines and their metabolites [Brodie ct al.. 1971: Carlsson et al.…”

Section: Pharmacologic Substancesmentioning

confidence: 99%

Pharmacologic Properties of the Internal Clock Underlying Time Perception in Humans

Rammsayer

Vogel

1992

Neuropsychobiology

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Performance on temporal discrimination of time intervals in the range of milliseconds is interpreted by the assumption of an internal clock; the higher the clock rate the better the temporal resolution of the internal clock will be, which is equivalent to more accuracy in timing of brief intervals. Although there is some evidence from animal and human studies suggesting that the clock rate depends on the effective level of brain dopamine (DA), the findings are not conclusive. Therefore, an alternative interpretation of the pharmacologic properties of the internal clock has been introduced. According to this interpretation, the internal timing mechanism can be seen as a biological rhythm that is susceptible to chronomutagenic agents, i.e., pharmacologic compounds that are able to produce an alteration in the period of a biological rhythm. To elucidate the pharmacologic properties of the internal timing mechanism, in a double-blind study either 1750 mg of the DA antagonist alpha-methy-p-tyro-sine (AMPT), 0.65 g/kg ethanol which possesses chronomutagenic effects, or placebo were applied to 80 male subjects. As measures of performance, difference threshold estimates in relation to a 50- and a 1,000-ms standard interval and respective response latencies were computed. Furthermore, urinary levels of DA, DOPAC, and HVA were quantified by HPLC analysis. Although AMPT treatment resulted in a pronounced reduction of more than 50% for DA, DOPAC, and HVA, temporal discrimination was not affected. On the other hand, ethanol induced a significant impairment in performance on temporal discrimination in the range of milliseconds as compared to placebo. Neither temporal discrimination in the range of seconds nor response latencies were affected by the drugs applied in this experiment. Our findings suggest that the internal timing mechanism underlying temporal discrimination of intervals in the range of milliseconds is independent of the effective level of brain DA. More likely, pharmacologically induced changes in clock rate appear to depend on the chronomutagenic effects of the drug applied. Furthermore, the absence of ethanol-induced changes in performance on temporal discrimination of longer intervals in the range of seconds supports the assumption of two distinct timing mechanisms underlying temporal discrimination in the millisecond and second range.

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Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

Cited by 56 publications

References 29 publications

Acebutolol in hypertension‐double‐blind trial against placebo.

Acebutolol in hypertension‐double‐blind trial against placebo.

Human norepinephrine metabolism

Pharmacologic Properties of the Internal Clock Underlying Time Perception in Humans

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