Nifedipine Improves Endothelial Function

Abstract

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 (nϭ37) 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 CD34ϩCD133ϩ 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 CD34ϩCD133ϩ 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 CD34ϩCD133ϩ 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. (Hypertension. 2008;52:491-498.)

Reactive oxygen species and vascular biology: implications in human hypertension

“…178,179 Some of the beneficial effects of classical antihypertensive agents such as -adrenergic blockers, angiotensin-converting enzyme inhibitors, AT 1 receptor antagonists and Ca 2+ channel blockers may be mediated, in part, by decreasing vascular oxidative stress. [180][181][182][183][184] These effects have been attributed to direct inhibition of NADPH oxidase activity and to intrinsic antioxidant properties of the drugs.…”

Lipid Peroxidation and Antioxidants in Arterial Hypertension

“…Furthermore, there is evidence that lowering blood pressure per se causes reduction of oxidative stress and improvement in endothelial function [92]. Several antihypertensive drugs with distinct mechanisms of action have been shown to decrease oxidant biomarkers in experimental and human hypertension [93][94][95]. However, there is limited evidence supporting the use of antioxidants to lower blood pressure in human hypertensive patients [5,92].…”

T-Type Ca2+ Channel Blockers Increase Smooth Muscle Progenitor Cells and Endothelial Progenitor Cells in Bone Marrow Stromal Cells in Culture by Suppression of Cell Death

“…Mibefradil contributes to biophysical interactions with the cell membrane that underlie antioxidant and cytoprotective activities in models of oxidative stress. 19) However, the protective mechanism of mibefradil against BMSC death may not depend upon direct cytoprotective effects against oxidative stress, because the L-type Ca 2+ channel blocker nifedipine, which is also known to have an antioxidative stress effect, 23,24) did not show a protective effect against BMSC death. Therefore, the protection mechanism of mibefradil may, at least in part, be due to the suppression of T-type Ca 2+ channel current.…”