| First Author | Buys ES | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 6 | Pages | 2316-25 |
| PubMed ID | 22565307 | Mgi Jnum | J:188294 |
| Mgi Id | MGI:5440136 | Doi | 10.1172/JCI60119 |
| Citation | Buys ES, et al. (2012) Genetic modifiers of hypertension in soluble guanylate cyclase alpha1-deficient mice. J Clin Invest 122(6):2316-25 |
| abstractText | 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 alpha1 subunit of soluble guanylate cyclase (sGCalpha1), 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 sGCalpha1 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 sGCalpha1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling. |
