on July 21, 2008
Published online before print July 21, 2008, doi: 10.1161/HYPERTENSIONAHA.108.111914
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Submitted on February 11, 2008
From the Department of Cardiology (T.S., T.K., Y.K-B., Y.N., O.Y., T.M.), Nagoya University Graduate School of Medicine, Nagoya, Japan; Departments of Cardio-Renal Medicine and Hypertension (T.S., Y.D., G.K.), and Internal Medicine and Molecular Science (T.S., R.U.), Nagoya City University Graduate School of Medical Science, Nagoya, Japan; and the Department of Nephrology and Hypertension (T.J.R.), Leiden University Medical Center, Leiden, The Netherlands. * To whom correspondence should be addressed. E-mail: takahisa{at}med.nagoya-u.ac.jp
or murohara{at}med.nagoya-u.ac.jp.
Abstract—Nifedipine has been shown to improve endothelial function. Recent studies have indicated that endothelial function is correlated with the number of circulating endothelial progenitor cells (EPCs), but it is unclear whether nifedipine affects the number and function of EPCs. The aims of this study were to determine the effects of nifedipine on the number and function of EPCs and to investigate the relationship between improvement of endothelial function and EPC numbers in patients with hypertension. Stage 1 hypertensive men (n=37) were randomly divided into the nifedipine group and the control untreated group. The nifedipine group was administered slow-release nifedipine (20 mg) once daily. At baseline and after 4 weeks, flow-mediated dilation, blood pressure, biochemical data, and number of circulating CD34+CD133+ progenitor cells and EPCs were measured. The direct effects of nifedipine on EPC number and function were assessed in vitro. In the nifedipine group, flow-mediated dilation and the numbers of circulating CD34+CD133+ progenitor cells and EPCs were increased, along with a decrease of serum malondialdehyde low-density lipoprotein. The improvement of flow-mediated dilation by nifedipine was correlated with the increase of circulating CD34+CD133+ progenitor cells. Nifedipine also improved angiogenesis-related functions of EPCs (differentiation, migration, and resistance to oxidative stress) in vitro. Thus, nifedipine improved endothelial function and EPC function in stage 1 hypertensive subjects. The latter action may be mediated by reduction of oxidative stress and suppression of EPC apoptosis. These results demonstrate that nifedipine preserves endothelial integrity in patients with hypertension, at least partly, by enhancing EPC numbers and activity.
Revised on March 5, 2008
Nifedipine Improves Endothelial Function. Role of Endothelial Progenitor Cells
Tomonori Sugiura;
Key words: hypertension • endothelial function • endothelial progenitor cell • nifedipine • oxidative stress
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