| Is altered adrenal steroid biosynthesis a key intermediate phenotype in hypertension? | |
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MedLine Citation:
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PMID: 12654713 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Approximately 10% of patients with hypertension have a high ratio of aldosterone to renin, but the reason for this and the relationships among low-renin essential hypertension, elevation of the ratio, and true primary aldosteronism are unclear. We have previously reported that a polymorphism of the gene (C-to-T conversion at position -344) encoding aldosterone synthase is associated with hypertension, particularly in patients with a high ratio. However, the most consistent association with this variant is a relative impairment of adrenal 11beta-hydroxylation. In this review, we propose that altered conversion of deoxycortisol to cortisol leads to a subtle, chronic increase in adrenocortrophin drive to the adrenal cortex, with eventual development of hyperplasia. In combination with other genetic or environmental factors (such as dietary sodium intake), we suggest that this might be responsible for the long-term development of a resetting of the aldosterone response to angiotensin II, giving rise to the phenotype of hypertension with a raised ratio. In some subjects, this may progress further to true primary aldosteronism with a dominant adrenal nodule. Thus, there may be a genetically influenced continuum from hypertension with a normal ratio, through hypertension with a raised ratio, and primary aldosteronism. |
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Authors:
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John M C Connell; Robert Fraser; Scott MacKenzie; Eleanor Davies |
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Publication Detail:
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Type: Journal Article; Review Date: 2003-03-24 |
Journal Detail:
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Title: Hypertension Volume: 41 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-05-05 Completed Date: 2003-06-09 Revised Date: 2005-11-16 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 993-9 Citation Subset: IM |
Affiliation:
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MRC Blood Pressure Group, Division of Cardiovascular and Medical Sciences, University of Glasgow, Scotland. j.connell@clinmed.gla.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Glands
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metabolism* Aldosterone / biosynthesis* Aldosterone Synthase / genetics, metabolism Humans Hyperaldosteronism / complications Hypertension / etiology, genetics, metabolism* Phenotype Renin / metabolism Steroid 11-beta-Hydroxylase / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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52-39-1/Aldosterone; EC 1.14.15.4/Aldosterone Synthase; EC 1.14.15.4/Steroid 11-beta-Hydroxylase; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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