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

(2012) JOURNAL OF CLINICAL INVESTIGATION. 122(6). p.2316-2325
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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.
Keywords
BLOOD-PRESSURE REGULATION, QUANTITATIVE TRAIT LOCI, GENOME-WIDE ASSOCIATION, TGR(MREN2) 27 RATS, KNOCKOUT MICE, SMOOTH-MUSCLE-CELLS, KIDNEY-DISEASE, CONVERTING ENZYME, NITRIC-OXIDE SYNTHASE, RENIN-ANGIOTENSIN SYSTEM

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Chicago
Buys, Emmanuel S, Michael J Raher, Andrew Kirby, Mohd Shahid, David M Baron, Sarah R Hayton, Laurel T Tainsh, et al. 2012. “Genetic Modifiers of Hypertension in Soluble Guanylate Cyclase Α1-deficient Mice.” Journal of Clinical Investigation 122 (6): 2316–2325.
APA
Buys, E. S., Raher, M. J., Kirby, A., Shahid, M., Baron, D. M., Hayton, S. R., Tainsh, L. T., et al. (2012). Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice. JOURNAL OF CLINICAL INVESTIGATION, 122(6), 2316–2325.
Vancouver
1.
Buys ES, Raher MJ, Kirby A, Shahid M, Baron DM, Hayton SR, et al. Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice. JOURNAL OF CLINICAL INVESTIGATION. 2012;122(6):2316–25.
MLA
Buys, Emmanuel S, Michael J Raher, Andrew Kirby, et al. “Genetic Modifiers of Hypertension in Soluble Guanylate Cyclase Α1-deficient Mice.” JOURNAL OF CLINICAL INVESTIGATION 122.6 (2012): 2316–2325. Print.
@article{2138459,
  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 \ensuremath{\alpha}1 subunit of soluble guanylate cyclase (sGC\ensuremath{\alpha}1), 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 sGC\ensuremath{\alpha}1 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 sGC\ensuremath{\alpha}1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling.},
  author       = {Buys, Emmanuel S and Raher, Michael J and Kirby, Andrew and Shahid, Mohd and Baron, David M and Hayton, Sarah R and Tainsh, Laurel T and Sips, Patrick and Rauwerdink, Kristen M and Yan, Qingshang and Tainsh, Robert ET and Shakartzi, Hannah R and Stevens, Christine and Decaluw{\'e}, Kelly and Rodrigues-Machado, Maria da Gloria and Malhotra, Rajeev and Van de Voorde, Johan and Wang, Tong and Brouckaert, Peter and Daly, Mark J and Bloch, Kenneth D},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keyword      = {BLOOD-PRESSURE REGULATION,QUANTITATIVE TRAIT LOCI,GENOME-WIDE ASSOCIATION,TGR(MREN2) 27 RATS,KNOCKOUT MICE,SMOOTH-MUSCLE-CELLS,KIDNEY-DISEASE,CONVERTING ENZYME,NITRIC-OXIDE SYNTHASE,RENIN-ANGIOTENSIN SYSTEM},
  language     = {eng},
  number       = {6},
  pages        = {2316--2325},
  title        = {Genetic modifiers of hypertension in soluble guanylate cyclase \ensuremath{\alpha}1-deficient mice},
  url          = {http://dx.doi.org/10.1172/JCI60119},
  volume       = {122},
  year         = {2012},
}

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