Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol

Eisenhofer, Graeme; Goldstein, David S.; Ropchak, T G; Nguyen, Hung Q.; Keiser, Harry R.; Kopin, Irwin J.

doi:10.1016/0165-1838(88)90130-0

Cited by 99 publications

(34 citation statements)

References 19 publications

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“…In sympathetic nerves there is an age-related impairment in norepinephrine transporter action (14,15). A reduction in brain neuronal reuptake of norepinephrine in the elderly, effected by reducing intraneuronal metabolism of norepinephrine and facilitating extraneuronal metabolism, might perhaps be expected to reduce DHPG jugular overflow into the internal jugular veins and increase MHPG overflow (21,25), although there is disagreement on this point (7,8). Our findings, however, argue against the importance of a central defect in neuronal norepinephrine reuptake.…”

Section: Discussioncontrasting

confidence: 48%

“…In older men, based on 21 unlilateral internal JV samples, the corresponding ratios were similar, 1.0:4.0:9.3. This finding perhaps argues against the increased overflow of norepinephrine and metabolites from the brain being due to reduced cerebral neuronal reuptake of norepinephrine, which might disproportionately increase MHPG overflow and reduce DHPG overflow (21,25), although there is disagreement on this point (7,8). * P Ͻ 0.05.…”

Section: Resultsmentioning

confidence: 73%

“…This difference was not a consequence of hemodynamic influences on transmitter washout to the circulation, as coronary sinus plasma flows were similar, but in addition to increased cardiac sympathetic nerve firing, diminished neuronal reuptake of norepinephrine may have contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart, which is predominantly into cardiac sympathetic nerves (8,10), was lower in the older men: mean 72%, range 42-87%, compared with mean 83%, range 60-92% (P Ͻ 0.05, Mann-Whitney U-test). Cardiac norepinephrine spillover was unrelated to resting heart rate overall for both groups combined.…”

Section: Resultsmentioning

confidence: 98%

“…The relative patterns of metabolite overflow did not differ significantly, which perhaps argues against the mechanism of increased CNS norepinephrine in the elderly being reduction in neuronal norepinephrine reuptake. There is some evidence (21,25), although it is disputed (7,8), that reduction in brain neuronal reuptake of norepinephrine in the elderly would be expected to reduce DHPG jugular venous overflow and increase MHPG overflow.…”

Section: Resultsmentioning

confidence: 99%

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The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover

Esler

Hastings

Lambert

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

103

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The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover. Am J Physiol Regulatory Integrative Comp Physiol 282: R909-R916, 2002; 10.1152/ ajpregu.00335.2001.-Investigating aging effects on the sympathetic nervous system and ascertaining underlying central nervous system (CNS) mechanisms mediating sympathetic stimulation is clinically pertinent because of the possible interconnection of cardiovascular disease development with age-dependent sympathetic nervous changes. Because of previous evidence linking human CNS neuronal noradrenergic function and sympathetic activity, we investigated the influence of aging on brain norepinephrine turnover in 22 healthy men aged 20-30 yr and 16 healthy men aged 60-75 yr by measuring the internal jugular venous overflow of norepinephrine and its lipophilic metabolites. Sympathoneural and adrenal medullary function was also studied, using plasma catecholamine isotope dilution methodology and regional central venous sampling. In the older men there was increased norepinephrine turnover in suprabulbar subcortical brain regions, 317 Ϯ 50 ng/min compared with 107 Ϯ 18 ng/min in younger men. A differentiated sympathetic nervous activation was also present in older men. Overall, levels of both cardiac and hepatomesenteric norepinephrine spillover were directly correlated with subcortical norepinephrine turnover. These findings suggest that in sympathetic nervous activation accompanying aging, as has previously been demonstrated with the sympathetic nervous stimulation in human hypertension and heart failure, there is an underlying sympathoexcitatory influence of noradrenergic projections to suprabulbar subcortical regions. epinephrine; heart; kidneys; adrenal medulla THE FUNCTION OF THE HUMAN sympathetic nervous system is altered in important ways by aging. These changes involve both the properties of the adrenergic receptors and the outflow of sympathetic neural traffic to individual organs (32). Based in large part on subcutaneous multiunit microneurographic recording from sympathetic fibers distributed in the company of motor nerves (1, 28, 37) and on the measurement of the spillover of the sympathetic neurotransmitter norepinephrine to plasma (14,15,36), there is now unequivocal evidence that progressive sympathetic activation occurs with aging. This sympathetic stimulation appears to involve the sympathetic outflow to the heart, the skeletal muscle vasculature, and the gut and liver, but to exclude the kidneys (14, 15). The nature of the underlying disturbance in central nervous system (CNS) sympathetic control, however, remains unknown.The impetus for seeking to better understand the central nervous mechanisms by which aging causes sympathetic activation has come in part from recognition that in a variety of cardiovascular disorders, including cardiac failure, essential hypertension, and ventricular arrhythmias, for all of which incidence rises with age, the sympathetic nervous system is causally involved (11). Antiadrenergic drugs have co...

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Section: Discussioncontrasting

confidence: 48%

Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover

Esler

Hastings

Lambert

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

103

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“…This means that most of the norepinephrine produced and released by nerves is metabolized within the nerves themselves (Figure 2). Because monoamine oxidase (MAO) is the only catecholamine-metabolizing enzyme present in sympathetic nerves, the norepinephrine metabolized within these nerves is all converted to dihydroxyphenylglycol (DHPG) (11)(12)(13). As a consequence, the DHPG appearing in Figure 2 -Quantitative diagram showing neuronal and extraneuronal pathways of norepinephrine (NE) metabolism before and after entry into the bloodstream.…”

Section: Disposition Of Catecholamines Derived From the Sympatho-adrementioning

confidence: 99%

Plasma metanephrines: a novel and cost-effective test for pheochromocytoma

Eisenhofer

Walther

Keiser

et al. 2000

Braz J Med Biol Res

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Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well as in many others with suggestive symptoms or with a familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends importantly on biochemical evidence of excess catecholamine production by a tumor. Imperfect sensitivity and specificity of commonly available biochemical tests and the low incidence of the tumor among the tested population mean that considerable time and effort can be expended in confirming or ruling out pheochromocytoma in patients where the tumor is suspected. Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free metanephrines means that a normal test result reliably excludes all but the smallest of pheochromocytomas so that no other tests are necessary. Measurements of plasma free metanephrines, when systematically combined with other diagnostic procedures outlined in this review, provide a more efficient, reliable and cost-effective approach for diagnosis of pheochromocytoma than offered by previously available approaches.

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