No abstract

O besity prevalence is soaring in industrialized countries and progressively increasing in the developing world. Altered patterns of nutrition and reduction in work-related energy expenditure have led to obesity becoming a truly global health issue. The central thermodynamic formulation for the origins of obesity, a mismatched energy balance equation, with an excess of dietary calorie intake over body energy expenditure, is a first step in the understanding of this phenomenon but leaves the diverse causal issues unexplored.Dietary calorie intake is modified by multiple social, economic, and cultural issues. Similarly, the reduction in energy expenditure in recent decades has complex origins, deriving from demographic and social change, which includes thirdworld transition from a labor-intensive agricultural economy to an industrial base, the introduction of household labor-saving devices, the popularity of transportation modes not reliant on physical effort, and from changed recreational habits, particularly in childhood (computer games instead of physical games). The prevalence of childhood obesity is escalating, having whimsically but not entirely unrealistically been attributed to "potato chips and computer chips."Obesity and hypertension are intimately associated, and both very commonly coexist in individual patients with insulin resistance, hyperinsulinemia, and hyperlipidemia, this clustering of adverse health factors 1 being designated the metabolic syndrome. The pathophysiological mechanisms by which obesity leads to hypertension remain uncertain. Understanding these processes might, perhaps, provide a more rational basis for drug treatment of obesity-related hypertension. Attempts at reduction in body weight, although pivotal in the treatment of obesity-related hypertension, more often than not fail, so that antihypertensive drug therapy is often needed.This review analyses the proposition that obesity is characterized by activation of the sympathetic nervous system and that obesity-related hypertension is, in fact, neurogenic, being initiated and sustained by neural mechanisms. At one time, this idea would have been held to fly in the face of both reason and empirical evidence, because the sympathetic nervous system is thermogenic and promotes negative energy balance and weight loss, 2 and in earlier experimental models of obesity, sympathetic nervous activity was found to be suppressed. 3 Consideration of these earlier and very influential experimental models of obesity, many of which involved brain lesions inhibiting both sympathetic nervous outflow and satiety, will now be the starting point for this review. Hypothalamic Models of Experimental ObesityVentromedial hypothalamic injury in rats can cause obesity either with or without hyperphagia. 3,4 The observation that hypothalamic ablation can cause obesity without overeating, but associated with sympathetic nervous suppression, led Bray et al 3 to propose that the sympathetic nervous system underactivity commonly present in animal models of obesity...

Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.

Background and Purpose-Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only. Methods-We used an isotope dilution technique to estimate the magnitude and time course of sympathoadrenal activation in 18 subarachnoid patients. Results-Compared with 2 different control groups, the patients with subarachnoid hemorrhage exhibited an approximately 3-fold increase in total-body norepinephrine spillover into plasma within 48 hours after insult (3.2Ϯ0.3 and 4.2Ϯ0.7 versus 10.2Ϯ1.4 nmol/L; PϽ0.05 versus both). This sympathetic activation persisted throughout the 7-to 10-day examination period and was normalized at the 6-month follow-up visit. Conclusions-The present study has established that massive sympathetic nervous activation occurs in patients after subarachnoid hemorrhage. This overactivation may relate to the well-known cardiac complications described in subarachnoid hemorrhage. (Stroke. 2000;31:901-906.)

Abstract-Hypertension in normal-weight and obese individuals is characterized by activation of the sympathetic nervous system. Measurement of spillover of the sympathetic transmitter, norepinephrine, to plasma indicates that the regional pattern of sympathetic activation in the 2 "variants" of essential hypertension differs, excluding the heart in obesity-related hypertension. Whether sympathetic nerve firing characteristics also differ is unknown. We studied multiunit and single fiber sympathetic nerve firing properties in patients with normal-weight hypertension and obesity-related hypertension, comparing these with nerve characteristics in normal-weight and obese people with normal blood pressure. Both normal-weight hypertensive (nϭ10) and obese hypertensive (nϭ14) patients had increased total multiunit muscle sympathetic nerve activity compared with the normal-weight (nϭ11) and obese (nϭ11) people with normal blood pressure (65Ϯ4 versus 47Ϯ6 bursts per 100 heartbeats, PϽ0.01 in the normal-weight groups and 68Ϯ4 versus 53Ϯ3 bursts per 100 beats, PϽ0.01 in the obese groups). Sympathetic activation in normal-weight hypertension was characterized by increased firing rate of single vasoconstrictor fibers (70Ϯ8 versus 28Ϯ3 spikes per 100 beats; PϽ0.001), increased firing probability per heartbeat (39Ϯ3% versus 20Ϯ3%; PϽ0.001), and higher incidence of multiple spikes per heartbeat (30Ϯ4% versus 17Ϯ4%; PϽ0.05). Sympathetic activation in obesity-related hypertension differed, involving recruitment of previously silent fibers, which fired at a normal rate. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of both the firing characteristics of individual sympathetic fibers and the sympathetic outflows involved. The underlying central nervous system mechanism and the adverse consequences of the 2 modes of sympathetic activation may differ. (Hypertension. 2007;50:862-868.)

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.

Abstract-There is growing evidence that essential hypertension is commonly neurogenic and is initiated and sustained by sympathetic nervous system overactivity. Potential mechanisms include increased central sympathetic outflow, altered norepinephrine (NE) neuronal reuptake, diminished arterial baroreflex dampening of sympathetic nerve traffic, and sympathetic neuromodulation by angiotensin II. To address this issue, we used microneurography and radiotracer dilution methodology to measure regional sympathetic activity in 22 hypertensive patients and 11 normotensive control subjects. The NE transport inhibitor desipramine was infused to directly assess the potential role of impaired neuronal NE reuptake. To evaluate possible angiotensin sympathetic neuromodulation, the relation of arterial and coronary sinus plasma concentrations of angiotensin II to sympathetic activity was investigated. Hypertensive patients displayed increased muscle sympathetic nerve activity and elevated total systemic, cardiac, and renal NE spillover. Cardiac neuronal NE reuptake was decreased in hypertensive subjects. In response to desipramine, both the reduction of fractional transcardiac 3[H]NE extraction and the increase in cardiac NE spillover were less pronounced in hypertensive patients. DNA sequencing analysis of the NE transporter gene revealed no mutations that could account for reduced transporter activity. Arterial baroreflex control of sympathetic nerve traffic was not diminished in hypertensive subjects. Angiotensin II plasma concentrations were similar in both groups and were not related to indexes of sympathetic activation. Increased rates of sympathetic nerve firing and reduced neuronal NE reuptake both contribute to sympathetic activation in hypertension, whereas a role for dampened arterial baroreflex restraint on sympathetic nerve traffic and a peripheral neuromodulating influence of angiotensin II appear to be excluded. Key Words: hypertension, essential Ⅲ catecholamines Ⅲ sympathetic nervous system Ⅲ norepinephrine Ⅲ angiotensin II A lthough there is growing evidence that essential hypertension is commonly neurogenic 1,2 and is initiated and sustained by overactivity of the sympathetic nervous system, the precise causal mechanisms leading to sympathetic augmentation in hypertensive subjects are still poorly understood. Among others, possible mechanisms include increased sympathetic nerve firing rates, 1,2 altered neuronal norepinephrine (NE) reuptake, 3,4 diminished arterial baroreflex buffering of sympathetic nerve traffic, 5 and facilitation of NE release by neurohumoral factors such as angiotensin II. 6 These possibilities, however, have not yet been conclusively tested for in humans.To further address some of these issues, we combined microneurography, to measure sympathetic nerve firing rates, with relevant radiotracer methodology to comprehensively study systemic and regional kinetics of NE and its intraneuronal and extraneuronal metabolites. To directly assess whether decreased neuronal NE reuptake contributes ...

In accordance with the monoamine hypothesis, a deficit in brain norepinephrine and dopamine exists in patients with depressive illness. Moreover, the brains of these patients use an energy source other than glucose, a situation that is normalized following the acute pharmacological blockade of the norepinephrine transporter with the tricyclic antidepressant, desipramine.