| First Author | Hassanain HH | Year | 2007 |
| Journal | Antioxid Redox Signal | Volume | 9 |
| Issue | 1 | Pages | 91-100 |
| PubMed ID | 17115888 | Mgi Jnum | J:150479 |
| Mgi Id | MGI:3850831 | Doi | 10.1089/ars.2007.9.91 |
| Citation | Hassanain HH, et al. (2007) Hypertension caused by transgenic overexpression of Rac1. Antioxid Redox Signal 9(1):91-100 |
| abstractText | Reactive oxygen species, including superoxide, are important mediators of the pathophysiology of hypertension. In the vasculature, superoxide antagonizes nitric oxide (NO*), resulting in increased vascular tone. The GTP binding protein Rac regulates a wide variety of cellular functions, including the activation of NADPH oxidase, the major source of O2*-in the blood vessel wall. An hypothesis is that Rac1 may act as an important regulator of vascular O2*- production, contributing to the balance between O2*- and NO* and maintaining consequent homeostasis of blood pressure. To alter the activity of vascular NADPH oxidase, the authors developed a transgenic animal model that overexpresses the human cDNA of the constitutively active mutant of Rac1 (RacCA) in smooth muscle cells using the smooth muscle +/--actin promoter. The RacCA transgenic had excessive amounts of O2*- in the vessel wall that, which led to heightened production of peroxynitrite, as detected by increased protein nitration and reduced NO* levels. RacCA mice developed moderate hypertension, which was corrected by N-acetyl-L-cysteine (NAC). RacCA transgenic mice also developed left ventricular hypertrophy as a secondary effect of pressure overload. The data suggest that Rac1 is a critical regulator of the redox state of blood vessels and homeostasis of blood pressure. |
