Document Detail


High blood pressure management: potential benefits of I1 agents.
MedLine Citation:
PMID:  9747906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SYMPATHETIC NERVOUS SYSTEM AND HYPERTENSION: Biochemical, electrophysiological, pharmacological and haemodynamic findings support the existence of sympathetic nervous system activation in primary human hypertension. Analysis of regional sympathetic nervous system function, using both neurophysiological methods for measuring sympathetic nerve firing rates, and neurochemical techniques for quantifying regional noradrenaline spillover to plasma has demonstrated activation of the sympathetic nervous outflows to the heart, the kidneys, and skeletal muscle vasculature, particularly in younger patients. The initiating cause of this sympathetic nervous stimulation is unknown, but estimation of central nervous system noradrenaline turnover in hypertensive patients, using measurements of the washout of noradrenaline and its lipophilic metabolites into the internal jugular veins, indicates that activation of forebrain pressor noradrenergic nuclei is the probable underlying mechanism. CONSEQUENCES OF INCREASED SYMPATHETIC ACTIVITY: The sympathetic activation present in human hypertension no doubt contributes to the blood pressure elevation, and is a legitimate target for therapeutic intervention with imidazoline receptor-binding agents such as rilmenidine. In addition, the sympathetic nervous activation seems to have adverse consequences in hypertensive patients beyond initiating the blood pressure elevation. There is evidence that neural vasoconstriction has metabolic effects, in skeletal muscle impairing glucose delivery to muscle, causing insulin resistance and hyperinsulinaemia, and in liver retarding postprandial clearing of lipids, contributing to hyperlipidaemia. Cardiac sympathetic activation is demonstrably a cause of sudden death in heart failure patients; a comparable arrhythmogenic effect is probable in hypertension. A trophic effect of sympathetic activation on cardiovascular growth is also likely, contributing to the development of left ventricular hypertrophy. Rilmenidine, through its central nervous system actions, has been demonstrated to powerfully reduce sympathetic nervous activity in essential hypertension patients. INHIBITING THE SYMPATHETIC SYSTEM: As the clinical consequences of sympathetic nervous activation in essential hypertension appear to go beyond that of hypertension pathogenesis, extending to a causal influence in atherosclerosis development, cardiovascular hypertrophy and cardiac arrhythmias, it is possible that, of all antihypertensive drugs, those inhibiting the sympathetic nervous system might best reduce cardiovascular risk. This remains to be tested.
Authors:
M Esler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of hypertension. Supplement : official journal of the International Society of Hypertension     Volume:  16     ISSN:  0952-1178     ISO Abbreviation:  J Hypertens Suppl     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-12-04     Completed Date:  1998-12-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8501422     Medline TA:  J Hypertens Suppl     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  S19-24     Citation Subset:  IM    
Affiliation:
Baker Medical Research Institute, Melbourne, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Antagonists / therapeutic use
Animals
Antihypertensive Agents / metabolism*,  therapeutic use*
Humans
Hypertension / drug therapy*,  physiopathology
Imidazoline Receptors
Receptors, Drug / metabolism*
Sympathetic Nervous System / drug effects,  physiopathology
Chemical
Reg. No./Substance:
0/Adrenergic Antagonists; 0/Antihypertensive Agents; 0/Imidazoline Receptors; 0/Receptors, Drug

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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