Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice.

The Journal of Clinical Investigation
Emmanuel BuysK D Bloch

Abstract

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.

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Citations

Dec 13, 2012·Current Hypertension Reports·Robrecht ThoonenEmmanuel S Buys
Nov 22, 2013·PloS One·Johannes StegbauerEvanthia Mergia
Apr 1, 2013·Annals of Neurosciences·Emmanuel S BuysBruce R Ksander
Jul 12, 2013·American Journal of Respiratory and Critical Care Medicine·Constantinos GlynosGuy G Brusselle
Jun 13, 2013·Trends in Cardiovascular Medicine·Patrick Y Sips, Emmanuel S Buys
Jun 7, 2014·Frontiers in Molecular Neuroscience·Emmanuel S BuysBruce R Ksander
Mar 24, 2018·International Journal of Molecular Sciences·Evanthia MergiaJohannes Stegbauer
Nov 6, 2014·Circulation. Cardiovascular Genetics·Martin R WilkinsMichael A Marletta
Oct 21, 2016·Physiological Genomics·Seung Kyum KimMichael P Massett
Jan 17, 2014·American Journal of Physiology. Renal Physiology·Rudolf Pullmann, Hamid Rabb
Jan 30, 2015·The Journal of Physiology·Dieter GronebergAndreas Friebe
Sep 30, 2020·International Journal of Molecular Sciences·Felke SteijnsPatrick Sips
May 21, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Ana C DordeaEmmanuel S Buys
May 21, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Adrian J Hobbs
Jan 15, 2014·Current Opinion in Nephrology and Hypertension·Emmanuel Buys, Patrick Sips
Nov 13, 2018·EBioMedicine·Xiqun ChenUNKNOWN Parkinson Study Group (PSG) The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) investigators

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Methods Mentioned

BETA
PCR
genotyping
ELISA
urine collection

Software Mentioned

MegAlign
ENSEMBL
qtl
AssayDesigner
SpectroTYPER
DNASTAR

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