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Biomedical subjects

G W Lambert

Publications and source records attributed to G W Lambert.

At least 19 recordsLinked to original sources
PubMed2004

The role of catecholamines in memory impairment in chicks following reduced gas exchange in ovo.

We have shown previously that reducing gas exchange to chick embryos by half wrapping eggs with an impermeable membrane from either days 14-18 (W14-18) or days 10-18 (W10-18) of the 21 day incubation results in post-hatch memory deficits. In the W10-18 chicks, short-term memory following training is impaired, whereas in the W14-18 chicks, memory is intact for 30 min but does not consolidate into long-term storage. The reduction in gas exchange caused by half wrapping eggs resulted in alterations in hematocrit, O2 and CO2 tensions suggesting that the embryos are hypoxic and hypercapnic. Our aim was to test the hypothesis that increases in circulating levels of catecholamines in ovo, as a result of hypoxia, lead to a disturbance of the central noradrenergic pathways resulting in cognitive impairment. Noradrenaline is critical for memory consolidation and a disturbance during development could compromise cognitive ability. In the present study, plasma noradrenaline levels were significantly elevated compared with control levels 2 days after hatch in W14-18 chicks. There was also a decrease in tissue noradrenaline concentration in the anterior forebrain in both W14-18 and W10-18 chicks. The differential ability of centrally administered beta2- and beta3-adrenoceptor agonists to overcome the memory deficit post-training, suggests altered responsiveness of central beta2-adrenoceptors to noradrenaline in W14-18 chicks. By comparing the W10-18 and W14-18 chicks with those from eggs wrapped from W10-14 we show that it is the timing of the prenatal hypoxia, rather than its duration, that determines the nature of cognitive dysfunction. We conclude that prenatal hypoxia induced by restriction of gas exchange can disrupt or alter central noradrenergic transmission causing cognitive impairment.

Adrenergic beta-2 Receptor Agonists↗
PubMed2003

Seasonal differences in the effect of isolation and restraint stress on the luteinizing hormone response to gonadotropin-releasing hormone in hypothalamopituitary disconnected, gonadectomized rams and ewes.

Stress responses are thought to act within the hypothalamopituitary unit to impair the reproductive system, and the sites of action may differ between sexes. The effect of isolation and restraint stress on pituitary responsiveness to GnRH in sheep was investigated, with emphasis on possible sex differences. Experiments were conducted during the breeding season and the nonbreeding season. In both experiments, 125 ng of GnRH was injected i.v. every 2 h into hypothalamopituitary disconnected, gonadectomized rams and ewes on 3 experimental days, with each day divided into two periods. During the second period on Day 2, isolation and restraint stress was imposed for 5.5 h. Plasma concentrations of LH and cortisol were measured in samples of blood collected from the jugular vein. In the second experiment (nonbreeding season), plasma concentrations of epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylglycol were also measured. In both experiments, there was no effect of isolation and restraint stress on plasma concentrations of cortisol in either sex. During the breeding season, there was no effect of isolation and restraint stress on plasma concentrations of LH in either sex. During the nonbreeding season, the amplitude of the first LH pulse after the commencement of stress was significantly reduced (P < 0.05) in rams and ewes. In the second experiment, during stress there was a significant increase (P < 0.05) in plasma concentrations of epinephrine in rams and ewes and significantly higher (P < 0.05) basal concentrations of norepinephrine in ewes than in rams. These results suggest that in sheep stress reduces responsiveness of the pituitary gland to exogenous GnRH during the nonbreeding season but not during the breeding season, possibly because of mediators of the stress response other than those of the hypothalamus-pituitary-adrenal gland axis.

Animals↗
PubMed2002

Effect of sunlight and season on serotonin turnover in the brain.

Alterations in monoaminergic neurotransmission in the brain are thought to underlie seasonal variations in mood, behaviour, and affective disorders. We took blood samples from internal jugular veins in 101 healthy men, to assess the relation between concentration of serotonin metabolite in these samples and weather conditions and season. We showed that turnover of serotonin by the brain was lowest in winter (p=0.013). Moreover, the rate of production of serotonin by the brain was directly related to the prevailing duration of bright sunlight (r=0.294, p=0.010), and rose rapidly with increased luminosity. Our findings are further evidence for the notion that changes in release of serotonin by the brain underlie mood seasonality and seasonal affective disorder.

Adolescent↗
PubMed2001

Paring down on Descartes: a review of brain noradrenaline and sympathetic nervous function.

1. The conceptual framework of mind-body interaction can be traced back to the seminal observations of the French philosopher and mathematician René Descartes (1596-1650). Descartes succeeded in eliminating the soul's apparent physiological role and established the brain as the body's control centre. 2. While the pivotal role played by the central nervous system (CNS) in the maintenance of physiological and psychological health has long been recognized, the development of methods designed for the direct examination of human CNS processes has only recently come to fruition. 3. There exists a substantial body of evidence derived from clinical and experimental studies indicating that CNS monoaminergic cell groups, in particular those using noradrenaline as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development and maintenance of the hypertensive state. 4. In essential hypertension, particularly in younger patients, there occurs an activation of sympathetic nervous outflows to the kidneys, heart and skeletal muscle. The existence of a correlation between subcortical brain noradrenaline turnover and total body noradrenaline spillover to plasma, resting blood pressure and heart rate provides further support for the observation that elevated subcortical noradrenergic activity subserves a sympathoexcitatory role in the regulation of sympathetic preganglionic neurons of the thorocolumbar cord.

Arteries↗
PubMed2000

Central nervous system norepinephrine metabolism in hypertension.

Although the pivotal role played by the brain in the maintenance of optimal physiologic and psychologic health has long been recognized, methods for the direct examination of human central nervous system processes have only recently been developed. A growing body of evidence indicates that central nervous systemmonoaminergic cell groups, in particular those utilizing norepinephrine as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development of the hypertensive state.

Adrenergic alpha-Agonists↗
PubMed2000

The 'adrenaline hypothesis' of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension.

OBJECTIVE: Whether adrenaline acts as a sympathetic nervous cotransmitter in humans and stimulates beta2-adrenoceptors to augment neuronal noradrenaline release remains a subject of considerable dispute. The aim of this study was to test if adrenaline is released from regional sympathetic nerves (in the heart) in patients with essential hypertension, and to investigate whether locally released adrenaline might enhance cardiac noradrenaline release. METHODS: Using dual isotope dilution methodology, adrenaline and noradrenaline plasma kinetics was measured for the whole body and in the heart in 13 untreated patients with essential hypertension and 27 healthy volunteers. All research participants underwent cardiac catheterization under resting conditions. RESULTS: At rest, there was negligible adrenaline release from the sympathetic nerves of the heart in healthy subjects, 0.27 +/- 1.62 ng/min. In contrast, in patients with essential hypertension, adrenaline was released from the heart at a rate of 1.46 +/- 1.73 ng/min, equivalent on a molar basis to approximately 5% of the associated cardiac noradrenaline spillover value. Cardiac noradrenaline spillover was higher in hypertensive patients, 24.9 +/- 17.0 ng/min compared to 15.4 +/- 11.7 ng/min in healthy volunteers (P< 0.05). Among patients, rates of cardiac adrenaline and noradrenaline spillover correlated directly (r= 0.59, P< 0.05). CONCLUSIONS: This study, in demonstrating release of adrenaline from the heart in patients with essential hypertension, and in disclosing a proportionality between rates of cardiac adrenaline and noradrenaline release, provides perhaps the most direct evidence to date in support of the 'adrenaline hypothesis' of essential hypertension.

Adult↗
PubMed1999

Catechol-O-methyltransferase activity in CHO cells expressing norepinephrine transporter.

1. We examined the existence of catecholamine metabolizing enzymes (catechol-O-methyltransferase, COMT, and monoamine oxidase, MAO) in CHO cells transfected with norepinephrine (NE) transporter (NET) cDNA. 2. NET activity was studied by incubating cells with [3H]-NE (0. 5 microCi ml-1, 20 min) in a Na+ containing medium. Incubation with [3H]-NE lead to [3H] accumulation at 47797+/-4864 d.p.m. per well. Specific inhibitors of NET abolished this uptake. 3. During post-uptake incubation, [3H] leaked rapidly from cells and the extracellular phase comprised 89% of total radioactivity within 40 min. Both [3H] retention and [3H] 'leakage' were largely unaffected by inhibitors for MAO. In contrast, COMT inhibitors, U-0521 and Ro 41-0960, dose-dependently increased intracellular [3H]-NE retention with a maximal increase of 4.5 fold. The EC50 for Ro 41-0960 was 139-times lower than that of U-0521. U-0521 largely inhibited [3H] 'leakage' and doubled the apparent Vmax for [3H]-NE uptake. 4. Addition of U-0521 during uptake incubation increased intracellular NE content by 8 fold. Normetanephrine, the COMT-dependent metabolite of NE, was formed in large quantities during post-uptake incubation. U-0521 significantly inhibited the formation of NMN with an equal preservation of intracellular NE. 5. CHO cells expressing NET possess COMT activity, which is responsible for the metabolism of NE to form lipophilic metabolite normetanephrine. The apparent 'properties' of the NET function expressed in CHO cells changed, after inhibition of COMT, in such a way closer to that described in the native neuronal preparations.

Animals↗
PubMed1999

Human obesity is associated with a chronic elevation in brain 5-hydroxytryptamine turnover.

The afferent signals that evoke changes in energy intake with regard to body weight regulation are presumed to arise partly from body stores, with the most likely candidate being adipose tissue depots. However, clinical investigation of the neuronal circuitry involved in the central nervous system's processing of such satiety signals remains largely unexplored. Using percutaneously placed catheters in either the right or left internal jugular veins, we were able to quantify the release of central nervous system monoamine and indoleamine neurotransmitters in 64 weight-stable male subjects with varying degrees of adiposity. Veno-arterial plasma concentration differences and internal jugular blood or plasma flow were used, according to the Fick Principle, to quantify the amount of neurotransmitter stemming from the brain. By combining this technique with a noradrenaline and adrenaline isotope dilution method for examining neuronal transmitter release, we were able to examine the association between central nervous system neurotransmitters and efferent sympathetic nervous outflow and adrenomedullary function in human obesity. We found that brain 5-hydroxytryptamine (serotonin) turnover is chronically elevated in proportion to adiposity and is increased postprandially to a similar degree in lean and obese individuals. There was no difference in the degree of sympathetic nervous activity or rate of adrenaline secretion in the subjects examined. It therefore seems that in human obesity, in the face of a chronic elevation in peripheral satiety signals, brain serotonergic processes are switched on accordingly, but the subsequent physiological response involving a reduction in food intake, increased thermogenesis and sympathetic activity is in some way impeded.

Adult↗
PubMed1999

Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age.

OBJECTIVE: Epidemiological studies suggest that intrauterine growth restriction (IUGR) due to maternal undernutrition during pregnancy represents a major risk factor for hypertension and diabetes in adult age. However, placental insufficiency, rather than maternal malnutrition, is the main cause of IUGR in the Western world. We therefore studied the relationship between birth weight and adult blood pressure and glucose tolerance in an established animal model of placental insufficiency. DESIGN: IUGR was induced by uterine artery ligation in pregnant rats and the offspring were studied at 3-4 months of age. METHODS: In one subgroup of animals (n = 41, birth weight range 3.2-6.6 g) blood pressure was recorded over 72 h using telemetry and hypothalamic tissue levels of noradrenaline was measured. In another subgroup (n = 30, birth weight range 3.0-6.8 g) the activity of the sympathetic nervous system (SNS) was assessed by noradrenaline isotope dilution techniques and glucose tolerance determined by an intravenous glucose load. RESULTS: Adult blood pressure was independent of birth weight Haemodynamic responses of IUGR rats to moderate sound stress was unaltered. In male rats neither SNS activity, hypothalamic noradrenaline concentrations nor glucose tolerance was associated with birth weight In contrast, IUGR in female rats was associated with increased SNS activity, elevated fasting blood glucose as well as lower insulin and higher glucose levels in response to a glucose load. CONCLUSION: IUGR is not linked to an elevated blood pressure at 3-4 months of age in this model. However, in female rats, IUGR is associated with increased SNS activity and impaired glucose tolerance in adult life.

Animals↗
PubMed1998

Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.

BACKGROUND: The sympathetic nervous system has long been believed to be involved in the pathogenesis of panic disorder, but studies to date, most using peripheral venous catecholamine measurements, have yielded conflicting and equivocal results. We tested sympathetic nervous function in patients with panic disorder by using more sensitive methods. METHODS: Sympathetic nervous and adrenal medullary function was measured by using direct nerve recording (clinical microneurography) and whole-body and cardiac catecholamine kinetics in 13 patients with panic disorder as defined by the DSM-IV, and 14 healthy control subjects. Measurements were made at rest, during laboratory stress (forced mental arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in the laboratory setting. RESULTS: Muscle sympathetic activity, arterial plasma concentration of norepinephrine, and the total and cardiac norepinephrine spillover rates to plasma were similar in patients and control subjects at rest, as was whole-body epinephrine secretion. Epinephrine spillover from the heart was elevated in patients with panic disorder (P=.01). Responses to laboratory mental stress were almost identical in patient and control groups. During panic attacks, there were marked increases in epinephrine secretion and large increases in the sympathetic activity in muscle in 2 patients but smaller changes in the total norepinephrine spillover to plasma. CONCLUSIONS: Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder. Epinephrine is released from the heart at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks. Contrary to popular belief, the sympathetic nervous system is not globally activated during panic attacks.

Adrenal Medulla↗
PubMed1998

Human muscle sympathetic activity and cardiac catecholamine spillover: no support for augmented sympathetic noradrenaline release by adrenaline co-transmission.

1. Evidence from animal studies indicates that circulating adrenaline may be taken up into sympathetic nerves, facilitating the release of noradrenaline. To test whether adrenaline acts as a co-transmitter in humans we studied eight healthy men (aged 19-23 years) during isometric handgrip before and after an adrenaline infusion (1-3 micrograms/min for > 30 min). Sympathetic activity was assessed using radiotracer kinetic techniques to measure total and cardiac spillovers of noradrenaline and adrenaline, and microneurography to measure muscle sympathetic activity. 2. During the adrenaline infusion systolic blood pressure and heart rate increased significantly and diastolic blood pressure decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma noradrenaline concentrations, increased significantly. Muscle sympathetic nerve traffic increased both during and after the end of the infusion. 3. Thirty minutes after the end of the adrenaline infusion there was adrenaline release from the heart (1.5 +/- 0.4 ng/min, mean +/- S.E.M.) indicating that significant adrenaline loading of cardiac sympathetic nerves had occurred. At this time muscle sympathetic nerve traffic and total body and cardiac noradrenaline spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve traffic 24 +/- 4 versus 21 +/- 3 bursts/min; total noradrenaline spillover 698 +/- 98 versus 618 +/- 119 ng/min; cardiac noradrenaline spillover 16.2 +/- 2.8 versus 13.9 +/- 3.9 ng/min). 4. Isometric handgrip contraction evoked similar responses pre- and post-adrenaline infusion in total and cardiac noradrenaline spillovers and in muscle sympathetic activity. 5. The results do not support the theory that adrenaline is a co-transmitter facilitating noradrenaline release from human sympathetic nerves.

Adult↗
PubMed1998

Internal jugular venous spillover of noradrenaline and metabolites and their association with sympathetic nervous activity.

It is recognized that the brain plays a pivotal role in the maintenance of blood pressure and the control of myocardial function. By combining direct sampling of internal jugular venous blood with a noradrenaline isotope dilution method, for examining neuronal transmitter release, and microneurographic nerve recording, we were able to quantify the release of central nervous system noradrenaline and its metabolites and investigate their association with efferent sympathetic nervous outflow in healthy subjects and patients with pure autonomic failure. To further investigate the relationship between brain noradrenaline, sympathetic nervous activity and blood pressure regulation we examined brain catecholamine turnover, based on the internal jugular venous overflow of noradrenaline and its principal central nervous system metabolites, in response to a variety of pharmacological challenges. A substantial increase was seen in brain noradrenaline turnover following trimethaphan, presumably resulting from a compensatory response in sympathoexcitatory forebrain noradrenergic neurones in the face of interruption of sympathetic neural traffic and reduction in arterial blood pressure. In contrast, reduction in central nervous system noradrenaline turnover accompanied the blood pressure fall produced by intravenous clonidine administration, thus representing the blood pressure lowering action of the drug. Following vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline turnover increased in parallel with elevation in muscle sympathetic nervous activity. While it is difficult to assess the source of the noradrenaline and metabolites determined in our studies, available evidence implicates noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5 region and the locus coeruleus as being involved in the regulation of sympathetic outflow and autonomic cardiovascular control.

Adolescent↗
PubMed1998

Influence of voluntary exercise on hypothalamic norepinephrine.

We combined hypothalamic tissue and plasma determinations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol with measurements of abdominal fat in voluntary running rats to examine the relationship among exercise training, hypothalamic and sympathetic nervous function, and body fat stores. The hypothalamic concentrations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol were reduced after exercise training (P < 0.01), with the amount of norepinephrine being strongly associated with the plasma norepinephrine (r = 0.58, P < 0.05) and dihydroxyphenylglycol (r = 0.65, P = 0.01) concentrations. Exercise training resulted in a diminution in abdominal fat mass (P < 0.01). A strong relationship existed between fat mass and hypothalamic norepinephrine content (r = 0.83, P < 0.001). The presence of a positive relationship between the arterial and hypothalamic norepinephrine levels provides presumptive evidence of an association between noradrenergic neuronal activity of the hypothalamus and sympathetic nervous function. The observation that abdominal fat mass is linked with norepinephrine in the hypothalamus raises the possibility that alterations in body fat stores provide an afferent signal linking hypothalamic function and the activity of the sympathetic nervous system.

Abdomen↗
PubMed1997

Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous activity in healthy human subjects.

Studies using internal jugular vein blood sampling in human subjects have demonstrated the release of noradrenaline from the brain and have provided a link between central nervous system noradrenergic neuronal activity and renal, cardiac and total body sympathetic activity. The aim of this study was to further categorise the dependence of regional sympathetic nervous function on central nervous system noradrenergic neuronal processes by combining measures of internal jugular venous noradrenaline spillover, as an indicator of brain noradrenaline release, and cerebral blood flow scans with measures of the overall integrated neuronal firing rate for the body as a whole, the spillover of noradrenaline into the coronary sinus and with measurements of resting muscle sympathetic nerve activity. Positive veno-arterial plasma noradrenaline gradients were found across the brain, with the plasma concentration being 17 +/- 3% (p < 0.01) greater in the internal jugular vein. Linear regression analysis revealed a significant relationship between the degree of muscle sympathetic nerve activity and the spillover of noradrenaline from subcortical brain regions (y = 0.1 x + 16.0; r = 0.81, p < 0.02). The rate of spillover of noradrenaline for the body as a whole also bore a significant association with the rate of subcortical noradrenaline spillover (y = 0.01x + 2.33; r = 0.71, p < 0.05). Cortical noradrenaline spillover was not related to any of the sympathetic nervous system parameters measured in this study. The demonstration of a direct relationship between the rate of peroneal nerve firing and the spillover of noradrenaline from subcortical brain regions provides further support for the concept of central nervous system noradrenergic cell groups behaving in a sympathoexcitatory role.

Adult↗
PubMed1997

Region-specific neuropeptide Y overflows at rest and during sympathetic activation in humans.

Neuropeptide Y coexists with norepinephrine in sympathetic nerves and is coreleased into the circulation on sympathetic activation. Little is known about the regional release of neuropeptide Y in humans under normal conditions or in pathophysiological situations of sympathetic activation or denervation. We measured plasma neuropeptide Y-like immunoreactivity and norepinephrine concentrations in samples taken from the brachial artery; coronary sinus; and internal jugular, antecubital, or hepatic veins in volunteers aged 20 to 64 years. Regional neuropeptide Y overflow at rest was calculated from venoarterial plasma concentration differences and plasma flow, and norepinephrine spillover was determined by [3H]norepinephrine infusion techniques. Cardiac release of neuropeptide Y and norepinephrine was examined in response to various stressors as well as in clinical models of sympathetic activation, cardiac failure, and denervation after cardiac transplantation. In healthy volunteers, cardiac, forearm, and jugular venous sample neuropeptide Y concentrations were similar to arterial levels. Hepatic vein plasma neuropeptide Y was greater than arterial both at rest (119 +/- 5% of arterial, n = 7) and after a meal (132 +/- 12%, n = 7), with neuropeptide Y overflows of 6 +/- 2 and 11 +/- 2 pmol/min, respectively. In contrast, hepatomesenteric norepinephrine spillover was not significantly increased by feeding. Although coronary sinus plasma norepinephrine concentrations increased significantly with the cardiac sympathetic activation accompanying mental arithmetic, coffee drinking, isotonic exercise, and bicycle exercise, only the latter powerful sympathetic stimulus increased neuropeptide Y overflow. Cardiac failure was associated with increased resting release of both norepinephrine and neuropeptide Y from the heart, whereas postcardiac transplant norepinephrine spillover from the heart was reduced. The net overflow of neuropeptide Y to plasma observed at rest across the hepatic circulation, but not the cardiac, forearm, or cerebral circulations, indicates that the gut, the liver, or both make a major contribution to systemic plasma neuropeptide Y levels in humans. Sympathetic activation by exercise produced a modest increase in cardiac neuropeptide Y overflow but to only approximately 25% of the resting input from the gut and without a change in arterial neuropeptide Y concentration. Plasma neuropeptide Y measurements are less sensitive than those of plasma norepinephrine concentrations as an index for quantifying sympathetic neural responses regulating the systemic circulation.

Adult↗
PubMed1996

Cerebral metabolism and its relationship with sympathetic nervous activity in essential hypertension: evaluation of the Dickinson hypothesis.

OBJECTIVE: To examine Dickinson's hypothesis in mild essential hypertension, in which neurogenic mechanisms are believed to be particularly relevant, by combining measures of cerebral oxygen consumption with the concurrent assessment of sympathetic nervous activity. DESIGN AND METHODS: Twenty-five untreated essential hypertensive subjects and 28 healthy age-matched volunteers underwent direct blood sampling using percutaneously inserted catheters advanced into the internal jugular vein, with cerebral blood flow scans to differentiate between cortical and subcortical venous drainage of the brain. Venoarterial blood gas measurements and internal jugular vein blood flows were used to calculate cerebral respiratory quotients and cerebral oxygen utilization. The total body rate of noradrenaline spillover into plasma was measured to assess relationships between cerebral oxidative metabolism and sympathetic nervous activity. RESULTS: Compared with controls, the hypertensive subjects exhibited reductions in internal jugular vein blood flow (482 +/- 29 versus 410 +/- 15 ml/min), cerebral oxygen consumption (27 +/- 2 versus 23 +/- 1 ml/min) and cerebral oxygen supply (93 +/- 6 versus 78 +/- 3 ml/min). The cerebral respiratory quotients were identical (1.00 +/- 0.04 in normotensives and 0.98 +/- 0.03 in hypertensives). Technetium blood flow scans revealed that the reductions in internal jugular blood flow and cerebral oxygen consumption in the hypertensive patients were confined to cortical brain regions. Cortical blood flow was quantitatively linked to the matching respiratory quotient and oxygen consumption, neither of which bore any relation to the level of sympathetic nervous activity. The spillover of noradrenaline into the plasma for the body as a whole did not differ between the two groups. CONCLUSIONS: In accord with Dickinson's hypothesis, we have established a reduction in internal jugular vein blood flow and cerebral oxygen utilization in hypertension. These reductions were confined to cortical brain regions. However, cerebral respiratory quotients in our hypertensive study group were no different from those in our controls, suggesting that glucose remained as the major cerebral metabolic substrate in hypertension. We were not able to establish a link between cerebral metabolism and blood pressure or sympathetic nervous activity in mildly hypertensive patients.

Adult↗
PubMed1995

Regional origins of 3-methoxy-4-hydroxyphenylglycol in plasma: effects of chronic sympathetic nervous activation and denervation, and acute reflex sympathetic stimulation.

The plasma level and urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal metabolite of noradrenaline in the brain, are often used as indicators of central nervous system noradrenergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma MHPG pool in 62 healthy volunteers. Veno-arterial plasma concentration differences and regional organ blood flows were used to quantify the relative amounts of MHPG contributed by various sites into plasma. Positive veno-arterial concentration gradients were found across the forearm, cardiac and jugular vessels in the healthy subjects. By far the majority of MHPG in plasma was derived from skeletal muscle, 5.3 +/- 1.8 nmol/min, with only minimal contribution (0.9 +/- 0.2 nmol/min) from the brain. Thus, to obtain an accurate indication of central nervous system noradrenergic activity the confounding influences of regional MHPG production must be excluded. 34 patients with chronic congestive heart failure, 6 patients with pure autonomic failure and 9 recent heart transplant recipients were used to investigate the possible effects of chronic sympathetic nervous system overactivity and sympathetic underactivity and denervation on peripheral MHPG production and plasma MHPG concentration. To examine the utility of plasma MHPG determinations as an indicator of acute alterations in sympathetic nervous activity we examined the influence of a variety of laboratory stressors on the arterial level and cardiac production of MHPG. The resting arterial plasma MHPG concentration mirrored sympathetic function in the patients with cardiac failure (sympathetic activation) and pure autonomic failure (sympathetic denervation), with mean MHPG plasma concentrations being 180 and 40% of those in healthy subjects. Cardiac MHPG production was increased in heart failure patients, and near zero with the cardiac sympathetic denervation accompanying transplantation and pure autonomic failure. In contrast, acute reflex stimulation of sympathetic nervous activity was not associated with parallel changes in the arterial level or cardiac production of MHPG. Measurements of peripheral plasma MHPG levels provide an index of prevailing sympathetic nervous function in clinical models of sympathetic overactivity and denervation, but are insensitive to acute sympathetic nervous system responses.

Adrenergic Uptake Inhibitors↗