Original papers: EndotheliumTreatment with valsartan stimulates endothelial progenitor cells and renal label-retaining cells in hypertensive ratsYoshida, Yoshinoria; Fukuda, Noborua,b; Maeshima, Akitoc; Yamamoto, Chiib; Matsumoto, Tarod; Ueno, Takahiroa; Nojima, Yoshihisac; Matsumoto, Koichia; Soma, Masayoshia Author Information aDivision of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Japan bAdvanced Research Institute of the Sciences and Humanities, Nihon University, Tokyo, Japan cDepartment of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Gunma, Japan dDivision of Cell Regeneration and Transplantation, Department of Advanced Medicine, Nihon University School of Medicine, Tokyo, Japan Received 22 April, 2010 Revised 7 August, 2010 Accepted 26 August, 2010 Correspondence to Noboru Fukuda, MD, PhD, Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173-8610, Japan Tel: +81 3 3972 8111; fax: +81 3 3972 8666; e-mail: [email protected] Journal of Hypertension: January 2011 - Volume 29 - Issue 1 - p 91-101 doi: 10.1097/HJH.0b013e32834000e2 Buy Metrics Abstract 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. © 2011 Lippincott Williams & Wilkins, Inc.