| First Author | Diao Z | Year | 2017 |
| Journal | Free Radic Biol Med | Volume | 106 |
| Pages | 80-90 | PubMed ID | 28189851 |
| Mgi Jnum | J:271846 | Mgi Id | MGI:6282222 |
| Doi | 10.1016/j.freeradbiomed.2017.02.021 | Citation | Diao Z, et al. (2017) Increased renal oxidative stress in salt-sensitive human GRK4gamma486V transgenic mice. Free Radic Biol Med 106:80-90 |
| abstractText | We tested the hypothesis that salt-sensitive hypertension is caused by renal oxidative stress by measuring the blood pressure and reactive oxygen species-related proteins in the kidneys of human G protein-coupled receptor kinase 4gamma (hGRK4gamma) 486V transgenic mice and non-transgenic (Non-T) littermates on normal and high salt diets. High salt diet increased the blood pressure, associated with impaired sodium excretion, in hGRK4gamma486V mice. Renal expressions of NOX isoforms were similar in both strains on normal salt diet but NOX2 was decreased by high salt diet to a greater extent in Non-T than hGRK4gamma486V mice. Renal HO-2, but not HO-1, protein was greater in hGRK4gamma486V than Non-T mice on normal salt diet and normalized by high salt diet. On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4gamma486V than Non-T mice and remained low on high salt diet. High salt diet decreased renal CuZnSOD in hGRK4gamma486V but not Non-T mice and decreased renal ECSOD to a greater extent in hGRK4gamma486V than Non-T mice. Renal SOD activity, superoxide production, and NOS3 protein were similar in two strains on normal salt diet. However, high salt diet decreased SOD activity and NOS3 protein and increased superoxide production in hGRK4gamma486V mice but not in Non-T mice. High salt diet also increased urinary 8-isoprostane and 8-hydroxydeoxyguanosine to a greater extent in hGRK4gamma486V than Non-T mice. hGRK4gammawild-type mice were normotensive and hGRK4gamma142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4gamma486V mice. Thus, hGRK4gamma486V causes salt-sensitive hypertension due, in part, to defective renal antioxidant mechanisms. |
