Imidazoline Receptor Agonists in Obesity-Related Hypertension: Therapeutic Targeting of the Sympathetic Nervous System

Author(s): Gavin W. Lambert, Kazuko Masuo.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)
(Formerly Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents)

Volume 10 , Issue 2 , 2010

Abstract:

Obesity, hypertension and obesity-related hypertension are growing health problems. Indeed, hypertension is an important risk factor for cardiovascular disease development, particularly in patients with obesity, diabetes, and metabolic disease. Obese subjects frequently present with hypertension, diabetes mellitus, metabolic disease, and end-organ damage (i.e. end-stage renal damage). In such patients, an integrated cardiovascular risk management approach should be adopted with aggressive blood pressure control being important in patients at high cardiovascular risk. The use of welltolerated antihypertensive agents with protective benefits beyond blood pressure lowering is advantageous. The identification and management of these cardiovascular risk factors are an important part of the overall management of hypertensive patients. Given that patients with obesity or metabolic syndrome are more predisposed to target organ damage, stringent targets for blood pressure control have been set in clinical guidelines; however clinical trial and real-life evidence suggest that these targets are difficult to achieve. The first line of treatment of obesity and metabolic syndrome is weight loss with a lifestyle modification, such as low caloric diet and exercise; however it is difficult to achieve and maintain weight loss. In severe cases, bariatric surgery may be an option, although whether surgery is associated with long term significantly sustained blood pressure reduction is problematic. Sympathetic nervous system activation and insulin resistance are recognized as being important in the pathogenesis of blood pressure elevation in essential hypertension, obesity and the metabolic syndrome. Angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs), which are known of the favorable effects on insulin resistance have therefore been widely used. Recently, several clinical and epidemiological studies have shown that the centrally acting imidazolin receptor agonists which inhibit sympathetic overflow from the brainstem, are highly efficacious, persistent, and well-tolerated antihypertensive agents. Additionally, imidazoline receptor agonists, such as moxonidine or rilmenidine, have been shown to exert beneficial effects not only on blood pressure, but also lipid (reducing free fatty acids) and carbohydrate metabolism (improving glucose tolerance), and neurohormonal parameters (norepinephrine, leptin). Given these additional benefits imidazolin receptor agonists may be a preferable treatment for obesity-related elevation in blood pressure and exert beneficial effects on metabolic and cardiovascular pathogenesis and end-organ damage. The topic of this chapter is central sympathetic nervous inhibition as a treatment for obesity-related hypertension with a particular focus on the possible use of “imidazoline receptor agonists”.

Keywords: Imidazoline receptor agonists, sympathetic nervous system, obesity, hypertension, obesity-related hypertension, metabolic syndrome, bariatric surgery, Angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, moxonidine, rilmenidine, coronary heart disease, rostral ventrolateral medulla, clonidine, hyperleptinemia, melanocortin pathway, baroreceptor dysfunction, tachycardia, 3-methoxy-4-hydroxyphenylglycol, 3, 4-dihydroxyphenylglycol, intracerebroventricular, splanchnic vascular beds, furosemide, pazosin, a-Adrenergic Receptor, Reserpine, a2-adrenoceptors, imidazoline-receptors, guanosine triphosphate, guanabenz, hyperglycemia, hypertrophy, glomerulosclerosis, euglycemic glucose clamp, amolopdipine, glucose tolerance, spontaneous hypertensive obese rats, radioligand, atrial natriuretic peptides, brain natriuretic peptides, antihypertensive therapy

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2010
Page: [59 - 65]
Pages: 7
DOI: 10.2174/187152210793177036
Price: $58

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