Treatment with valsartan stimulates endothelial progenitor cells and renal label-retaining cells in hypertensive rats

OBJECTIVE: The pathogenesis of hypertension is dependent on tissue angiotensin (Ang) II, which induces cardiovascular and renal remodeling. The presence of label-retaining cells (LRCs) as renal stem cells has been reported in nephrotubulus. We examined effects of treatment with valsartan on endothelial progenitor cells (EPCs) and renal LRCs in stroke-prone spontaneously hypertensive rats (SHR-SP). METHODS: SHR-SP were salt-loaded and treated with hydralazine or valsartan. Peripheral blood mononuclear cells (MNCs) were cultured to assess EPC colony formation and migration. LRCs were labeled for 1 week with bromodeoxyuridine (BrdU) and were detected after a 2-week chase period. We measured expression of c-kit and Pax-2 mRNAs in renal medulla. RESULTS: Colony formation and migration of EPCs were suppressed in salt-loaded SHR-SP. Treatment with valsartan markedly stimulated these EPC functions. There was no difference in the number of renal LRCs in normotensive Wistar-Kyoto rats and SHR-SP. Treatment with valsartan significantly improved renal tubular degeneration and increased the number of LRCs in renal medulla from salt-loaded SHR-SP. Treatment with valsartan significantly increased expression of c-kit and Pax-2 mRNAs in renal medulla from salt-loaded SHR-SP. CONCLUSION: These findings suggest that ARBs have cardiovascular and renal protective effects through an antioxidative action that stimulates ECP function and increases the number of the self-repairing renal LRCs.