Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice
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Author
Raher, Michael J.
Kirby, Andrew
Mohd, Shahid
Hayton, Sarah R.
Tainsh, Laurel T.
Rauwerdink, Kristen M.
Yan, Qingshang
Shakartzi, Hannah R.
Stevens, Christine
Decaluwé, Kelly
Rodrigues-Machado, Maria da Gloria
Van de Voorde, Johan
Wang, Tong
Brouckaert, Peter
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1172/JCI60119Metadata
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Buys, Emmanuel S., Michael J. Raher, Andrew Kirby, Shahid Mohd, David M. Baron, Sarah R. Hayton, Laurel T. Tainsh, et al. 2012. “Genetic Modifiers of Hypertension in Soluble Guanylate Cyclase Α1–deficient Mice.” J. Clin. Invest. 122 (6) (June 1): 2316–2325. doi:10.1172/jci60119.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366402/Terms of Use
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