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Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice
Emmanuel S. Buys, Michael J. Raher, Andrew Kirby, Mohd Shahid, 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, and Kenneth D. Bloch
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Published August 1, 2012 - More info
J Clin Invest. 2012;122(8):3024–3024. https://doi.org/10.1172/JCI65763.
© 2012 The American Society for Clinical Investigation
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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.
Authors
Emmanuel S. Buys, Michael J. Raher, Andrew Kirby, 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
Original citation: J. Clin. Invest. 2012;122(6):2316–2325. doi:10.1172/JCI60119.
Citation for this corrigendum: J. Clin. Invest. 2012;122(8):3024. doi:10.1172/JCI65763.
During the preparation of this manuscript, Mohd Shahid’s name was given incorrectly in the author list. The correct author list is above.
The authors regret the error.
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ISSN: 0021-9738 (print), 1558-8238 (online)