Involvement of imidazoline-preferring receptors in regulation of sympathetic tone

Sannajust, Frederick; Head, Geoffrey A.

doi:10.1016/0002-9149(94)90036-1

Cited by 28 publications

(9 citation statements)

References 39 publications

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“…The imidazoline binding agents produce the desired sympathetic inhibition in the skeletal muscle vasculature and kidneys. 97 Such an approach might be preferred on theoretical grounds, but at present there is little empirical evidence to support it.…”

Section: Is It Preferable That Antihypertensives Used In Obesity Hypementioning

confidence: 99%

Mechanisms of Sympathetic Activation in Obesity-Related Hypertension

et al. 2006

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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...

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Section: Is It Preferable That Antihypertensives Used In Obesity Hypementioning

confidence: 99%

Mechanisms of Sympathetic Activation in Obesity-Related Hypertension

et al. 2006

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“…Some antihypertensive drugs reduce whole-body sympathetic activity and total noradrenaline spillover as the mechanism of their blood pressurelowering action, formerly ganglion blockers (Mitchell et al 2009) and currently imidazoline central sympathetic inhibitors, such as moxonidine and rilmenidine (Sannajust & Head, 1994). With some antihypertensive drugs, including diuretics and dihydropyridine calcium channel blocking drugs, sympathetic activation occurs, which is a potentially adverse effect.…”

Section: E S L E Rmentioning

confidence: 99%

“…Perhaps centrally acing sympathetic suppressants, imidazoline binding agents such as moxonidine and rilmenidine, should be specifically prescribed in patients with essential hypertension? Both drugs produce the desired sympathetic inhibition in the sympathetic outflows to the heart, kidneys and skeletal muscle vasculature (Sannajust & Head, 1994). They are largely free of the side-effects of their progenitor, clonidine, but are currently underutilized in the medical management of hypertension.…”

Section: Hypertensionmentioning

confidence: 99%

The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension

Esler

2011

Experimental Physiology

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The 17th century London neuroanatomical school headed by Thomas Willis provided us with the first identifiable images of the sympathetic nervous system. Nineteenth century giants of European physiology (Bernard, Waller and Brown-Sequard) identified these as the 'pressor nerves'. Von Euler's demonstration that the sympathetic transmitter was noradrenaline brought the field into the modern era. The development of ganglion-blocking drugs by Paton, whose name this review commemorates, allowed comprehensive pharmacological antagonism of this system in patients. With the development of contemporary techniques for recording from human sympathetic nerves and quantifying rates of noradrenaline release, the sympathetic nervous system became accessible to clinical scientists investigating possible contributions to cardiovascular and other diseases. Sympathetic nervous system responses typically are regionally differentiated, with activation in one outflow sometimes accompanying no change or sympathetic inhibition in another. Regional sympathetic activity is best studied in humans by recording from postganglionic sympathetic efferents (multi-unit or single-fibre recording) and by isotope dilution-derived measurement of organ-specific noradrenaline release to plasma from sympathetic nerves (regional 'noradrenaline spillover'). With the application of these techniques, evidence has been assembled in the past three decades which indicates that sympathetic nervous system activation is crucial in the development of cardiovascular disorders, most notably heart failure and essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is mature in cardiac failure, with knowledge of cardiac neural pathophysiology having led to introduction of β-adrenergic blockers, an effective therapy. Perhaps we are now on the cusp of effective translation in patients with essential hypertension, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on prior demonstration in them of activation of the renal sympathetic outflow.

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“…Additionally, these agents bind to specific imidazoline (I) receptors in the rostral ventrolateral medulla, which are distinct from a-adrenergic receptors [65,68].…”

Section: Overviewmentioning

confidence: 99%