Article
Angiotensin II is genotoxic in renal tubular cells
Angiotensin II is genotoxic in renal tubular cells
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Published: | August 8, 2006 |
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In various forms of experimental hypertension the intrarenal concentration of angiotensin II is markedly enhanced as compared to its circulating levels. Since this octapeptide elicits the formation of proinflammatory cytokines and reactive oxygen species, we asked ourselves whether it induces DNA damage. Mutations of critical genes could, in the long-term, favour development of atherosclerosis and cancer.
Therefore, we measured the dose-dependent DNA-damaging effects of angiotensin II in two kidney cell lines: LLC-PK1 (proximal tubules, porcine) and HK-2 (proximal tubules, human) by comet assay and micronucleus frequency test. Production of oxidative stress by angiotensin II was analysed by flow cytometry. The presence of the AT1 receptor in the cell lines was evidenced by PCR.
Angiotensin II itself was shown to induce oxidative stress and in concentrations from 200 ng/ml caused DNA damage in both cell lines. The injury could be prevented by the addition of the antioxidant N-acetylcysteine and the AT1 receptor antagonist, candesartan. The AT1 blocker by itself showed no antioxidant capacity as tested by co-incubation with hydrogen peroxide-treated cells. By co-incubation with the angiotensin I converting enzyme inhibitor ramiprilat, the DNA damage could also be reduced, but to a lesser degree. Long-term clinical studies will show whether these in vitro data are transferable to humans