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Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications.
MedLine Citation:
PMID:  22048570     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.Hypertension Research advance online publication, 3 November 2011; doi:10.1038/hr.2011.173.
Authors:
Graziela Z Kalil; William G Haynes
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-03
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  -     ISSN:  1348-4214     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Divisions of Endocrinology and Cardiovascular Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
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