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Murray Esler

Publications and source records attributed to Murray Esler.

31 records · Page 2Linked to original sources
PubMed2003

Interactions between leptin and the human sympathetic nervous system.

Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1+/-1.2 vs 12.8+/-3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7+/-1.1 ng/mL vs 4.0+/-0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0+/-30.5 mL/min, compared with 56.9+/-18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.

Adult↗
PubMed2003

Hearts and minds.

Explore the source record for details and available documents.

Editorial↗
PubMed2003

Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure.

Although the widespread introduction of beta-adrenoceptor antagonists into the management of congestive heart failure (CHF) has led to significant improvements in morbidity and mortality, it is also apparent that clinical responses to this therapy vary substantially. With the recognition that functionally significant genetic polymorphisms of the beta2-adrenoceptor exist with clinically relevant allelic frequency, we hypothesized that beta2-adrenoceptor genotype may affect the response to carvedilol. The clinical response, influence on left ventricular function and beta2-adrenoceptor (beta2AR) genotype was determined in 80 patients treated with carvedilol. A clinically significant improvement in left ventricular function (good responder) was defined as an absolute improvement of 10% in the left ventricular ejection fraction or 5% in the fractional shortening. Consistent with studies performed in vitro on the influence of beta2AR genotype and receptor desensitization, subjects who were homozygous for the allele encoding the Gln27 polymorphism displayed a significantly lower proportion of good responders than patients who were homozygous or heterozygous for the Glu27 polymorphism (26% versus 63%, P=0.003). These data demonstrate a significant influence of beta2AR genotype in the response to carvedilol in CHF patients. Accordingly, determination of beta2AR status may be of value in the tailoring of individual therapy in patients with CHF.

Adrenergic beta-Antagonists↗
PubMed2003

Increased suicide rate in the middle-aged and its association with hours of sunlight.

OBJECTIVE: Aside from diminished daily functional capacity, individuals with depression are at greatly higher risk of suicide. Given that both endogenous depression severity and the incidence of suicide peak during the spring and summer months, it would seem that an environmental cue-one that generates alterations in brain neuronal activity that result in depressed affect or suicidal ideation-might be important. METHOD: The authors examined the frequency of suicide and its relation to meteorological factors in the state of Victoria between January 1990 and April 1999. RESULTS: The incidence of suicide had its nadir in winter and zenith in the spring and summer and paralleled closely the number of bright sunlight hours. This pattern was particularly marked for violent suicide. During the decade, the suicide rate significantly increased among men between 21 and 60 years of age and women between 41 and 60. CONCLUSIONS: The incidence of suicide in southeastern Australia displays a clear seasonal pattern, being positively linked with prevailing levels of sunlight. The rate of suicide increased in the latter half of the last decade.

Adult↗
PubMed2002

Dysautonomias: clinical disorders of the autonomic nervous system.

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities. In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after "patchy" autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops. Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with beta-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.

Autonomic Nervous System↗
PubMed2002

Influence of leptin on neurotransmitter overflow from the rat brain in vitro.

The 16-kDa polypeptide hormone, leptin along with the neurotransmitters noradrenaline and serotonin (5-HT) have important physiological roles in the regulation of a number of neuroendocrine actions particularly feeding. Leptin receptor mRNA and immunoreactivity has been reported in various brain regions, while recent studies suggest that leptin is released from the human brain. This study investigated the interactions between leptinergic and neurotransmitter systems of the rat brain in vitro. Techniques were established to simultaneously monitor the release of endogenous noradrenaline and its metabolite 3,4 dihydroxyphenylglycol (DHPG), and 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) from the rat brain. The neuromodulatory action of leptin (0.2 and 3 nM) on the overflow of noradrenaline and DHPG from the medulla and hypothalamus was examined. The effect of leptin on 5-HT and 5-HIAA overflow from the hypothalamus was also investigated. Administration of 0.2 and 3 nM leptin significantly increased medullary noradrenaline overflow to 172% and 174% of basal levels, respectively. Leptin had no significant effect on hypothalamic noradrenaline overflow, while leptin perfusion induced a significant increase in 5-HIAA overflow from the hypothalamus. This study lends support to the notion of a complex interaction of the leptinergic and brain neurotransmitters involved in the control of feeding and energy metabolism.

Animals↗
PubMed2002

Influence of ageing on the sympathetic nervous system and adrenal medulla at rest and during stress.

The influence of ageing on the sympathetic nervous system and adrenal medulla was studied neurochemically in humans, using isotopic dilution measurement of regional and whole body catecholamine release to plasma in humans. With ageing, sympathetic activation was evident in the heart, and the gut and liver at rest. The mechanism appeared to be by activation of sympathoexcitatory noradrenergic suprabulbar projections from the brainstem. Sympathetic nervous responses with stressors were augmented. Conversely, adrenal medullary release of epinephrine was subnormal in the elderly, at rest and during stress.

Adrenal Medulla↗
PubMed2002

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

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 +/- 50 ng/min compared with 107 +/- 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.

Adult↗
PubMed2002

Differentiation in the effects of the angiotensin II receptor blocker class on autonomic function.

Measurement of regional sympathetic activity with nerve recording and noradrenaline spillover isotope dilution techniques demonstrates activation of the sympathetic nerves of the heart, kidneys and skeletal muscle vasculature in younger patients with essential hypertension. Sympathetic overactivity in the renal sympathetic outflow is a prominent pathophysiological feature in obesity-related hypertensives of any age. This increase in sympathetic activity is thought to both initiate and sustain the blood pressure elevation, and, in addition, contributes to adverse cardiovascular events. Sympathetic overactivity seems to particularly influence systolic pressure, by increasing the rate of left ventricular ejection, by reducing arterial compliance through increasing neural arterial tone, and via arteriolar vasoconstriction, by promoting rebound of the reflected arterial wave from the periphery. Inhibition of the renin-angiotensin system in certain circumstances appears to be able to reduce sympathetic nervous activity. Claims have been made for such an action at virtually every site in the sympathetic neuraxis. In reality, renin-angiotensin actions on the sympathetic nervous system are probably much more circumscribed than this, with the case perhaps being strongest for a presynaptic action of angiotensin on sympathetic nerves, to augment noradrenaline release. The ability of angiotensin receptor blockers to antagonize neural presynaptic angiotensin AT1 receptors appears to differ markedly between the individual agents in this drug class. In experimental models, such as the pithed rat, neural presynaptic actions are particularly evident with eprosartan. In a blinded study of crossover design, the effects of eprosartan and losartan on sympathetic nerve firing, measured by microneurography, and whole body noradrenaline spillover to plasma is currently being measured in patients with essential hypertension. A reduction in noradrenaline spillover disproportionate to any possible fall in nerve firing would document the presence of presynaptic antagonism of noradrenaline release.

Angiotensin Receptor Antagonists↗