Document Detail

Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice.
MedLine Citation:
PMID:  22565307     Owner:  NLM     Status:  MEDLINE    
Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the α1 subunit of soluble guanylate cyclase (sGCα1), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGCα1 deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGCα1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling.
Emmanuel S Buys; Michael J Raher; Andrew Kirby; Mohd Shahid; Shahid Mohd; David M Baron; Sarah R Hayton; Laurel T Tainsh; Patrick Y Sips; Kristen M Rauwerdink; Qingshang Yan; Robert E T Tainsh; Hannah R Shakartzi; Christine Stevens; Kelly Decaluwé; Maria da Gloria Rodrigues-Machado; Rajeev Malhotra; Johan Van de Voorde; Tong Wang; Peter Brouckaert; Mark J Daly; Kenneth D Bloch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-08
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-08-20     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2316-25     Citation Subset:  AIM; IM    
Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Cyclic GMP / genetics,  metabolism
Endothelium, Vascular / enzymology
Genetic Linkage
Genome, Human*
Guanylate Cyclase / genetics*,  metabolism
Hypertension / enzymology,  genetics*
Mice, Knockout
Quantitative Trait Loci*
Receptors, Cytoplasmic and Nuclear / genetics*,  metabolism
Renin / genetics,  metabolism
Renin-Angiotensin System / genetics*
Second Messenger Systems / genetics*
Species Specificity
Vasodilation / genetics*
Grant Support
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 7665-99-8/Cyclic GMP; EC; EC Cyclase; EC guanylyl cyclase
Erratum In:
J Clin Invest. 2012 Aug 1;122(8):3024
Note: Mohd, Shahid [corrected to Shahid, Mohd]

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

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