Document Detail

Analysis of the role of angiotensinogen in spontaneous hypertension.
MedLine Citation:
PMID:  7768569     Owner:  NLM     Status:  MEDLINE    
Allelic variants at the human angiotensinogen locus have recently been reported to increase susceptibility to the development of essential hypertension. In this study we analyzed the role played by angiotensinogen in the elevated blood pressure of the spontaneously hypertensive rat (SHR). The SHR angiotensinogen locus (on chromosome 19) cosegregated with a significant (P = .003) and specific increase in pulse pressure in F2 rats derived from a cross of the SHR with the normotensive Wistar-Kyoto rat (WKY), accounting for 20% of the genetic (10% of total) variance in this phenotype. To identify potential mechanisms underlying the effect of the locus, we further examined angiotensinogen structure and expression in the two strains. Sequence analysis of the respective coding regions revealed no differences in the primary structure of angiotensinogen between the strains. Likewise, plasma angiotensinogen level did not differ in adult rats of the two strains. However, gene expression studies showed tissue-specific, age-related differences in angiotensinogen mRNA levels between SHR and WKY, particularly in the aorta. The findings suggest that pulse pressure, which significantly influences cardiovascular risk, has independent genetic determinants. They further suggest that the effect of the angiotensinogen locus on this phenotype in the SHR may be mediated through a tissue-specific abnormality of angiotensinogen gene expression.
D Lodwick; M A Kaiser; J Harris; F Cumin; M Vincent; N J Samani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  25     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-06-30     Completed Date:  1995-06-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1245-51     Citation Subset:  IM    
Department of Medicine, University of Leicester, Leicester Royal Infirmary, UK.
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MeSH Terms
Angiotensinogen / blood,  genetics,  physiology*
Base Sequence
Chromosome Mapping
Hypertension / etiology*,  genetics
Molecular Sequence Data
Polymorphism, Restriction Fragment Length
RNA, Messenger / analysis
Rats, Inbred SHR
Rats, Inbred WKY
Renin / blood
Reg. No./Substance:
0/RNA, Messenger; 11002-13-4/Angiotensinogen; EC

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