Document Detail


Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males.
MedLine Citation:
PMID:  17360661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adrenomedullin (AM) is a potent vasodilator peptide in plasma at picomolar levels. Polymorphisms in the human AM gene have been associated with genetic predisposition to diabetic nephropathy and proteinuria with essential hypertension, and numerous studies have demonstrated that endogenous AM plays a role in protecting the heart and kidneys from fibrosis resulting from cardiovascular disease. Elevated plasma levels of AM are associated with pregnancy and sepsis and with cardiovascular stress and hypertension. However, there are no reports of the effects of genetic differences in the expression of the endogenous AM gene and of gender on blood pressure in these circumstances or on the pathological changes accompanying hypertension. To address these questions, we have generated mice having genetically controlled levels of AM mRNA ranging from approximately 50% to approximately 140% of wild-type levels. These modest changes in AM gene expression have no effect on basal blood pressure. Although pregnancy and sepsis increase plasma AM levels, genetically reducing AM production does not affect the transient hypotension that occurs during normal pregnancy or that is induced by treatment with lipopolysaccharide. Nor does the reduction of AM affect chronic hypertension caused by a renin transgene. However, 50% normal expression of AM enhances cardiac hypertrophy and renal damage in male, but not female, mice with a renin transgene. These observations suggest that the effect of gender on the role of AM in counteracting cardiovascular damage in humans merits careful evaluation.
Authors:
Kathleen Caron; John Hagaman; Toshio Nishikimi; Hyung-Suk Kim; Oliver Smithies
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-03-15     Completed Date:  2007-06-13     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3420-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin / blood,  genetics,  metabolism*
Analysis of Variance
Animals
Blood Pressure
Cardiovascular Diseases / genetics,  metabolism*
Female
Gene Expression*
Male
Mice
Mice, Transgenic
Pregnancy
Sex Factors
Grant Support
ID/Acronym/Agency:
HD046970/HD/NICHD NIH HHS; HL49277/HL/NHLBI NIH HHS; R01 HL049277/HL/NHLBI NIH HHS; R01 HL049277-14/HL/NHLBI NIH HHS; R01 HL049277-15/HL/NHLBI NIH HHS; R01 HL049277-16/HL/NHLBI NIH HHS; R01 HL049277-17/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
148498-78-6/Adrenomedullin
Comments/Corrections

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


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