[Calcium antagonists: current and future applications based on new evidence. Pleiotropic effects of calcium channel blockers on vascular endothelial function].

Ample evidence has demonstrated that calcium channel blockers (CCBs) exert pleiotropic effects on vasculature, leading to restoring endothelial dysfunction and suppressing progression of atherosclerosis both in experimental and clinical settings. CCBs protect vasculature by various antioxidative mechanisms as follows : stimulating endothelial NO production and/or restoring decline in circulating adiponectin and HDL level. Moreover, CCBs has been also demonstrated to enhance circulating endothelial progenitor cell level, of which has been known to correlate to endothelial function. through its antioxidative property. Accordingly, these evidences suggest that CCB could be expected as another antiatherosclerotic remedy in patient population.

Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers.

BACKGROUND: Smoking is a major cardiovascular risk factor, leading to endothelial dysfunction. The present study investigated the hypothesis that pitavastatin, an HMG-CoA reductase inhibitor, may improve endothelial function in chronic smokers via its antioxidant properties. METHODS AND RESULTS: The 30 male chronic smokers who exhibited mild hypercholesterolemia at the time of physical check-up were enrolled and randomized to the pitavastatin group (2 mg/day, n=15) or the untreated control group (n=15). Before and after the 4-week treatment period, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent dilation by glyceryl trinitrate (GTD) were examined, and the FMD/GTD ratio was calculated. The pitavastatin group showed a significant restoration of endothelial function (percent change in FMD: +49.6% vs +1.4%; percent change in FMD/GTD ratio: +26.6% vs 4.5%, P<0.05 respectively), and a significant reduction in oxidative stress levels (malondialdehyde-low-density lipoprotein-cholesterol: 16.6% vs +7.5%; free radical activity: 1.8% vs +9.7%, P<0.05 respectively) compared with the control group. Pitavastatin had no effect on the number of circulating CD34(+)CD133(+) progenitor cells, endothelial progenitor cells, or the MMP-2, MMP-9 and VEGF levels. In vitro oxidative stress monitoring assay revealed that pitavastatin protected endothelial cells against oxidative stress. CONCLUSIONS: Pitavastatin restores endothelial function, even in chronic smokers, possibly through its antioxidative properties. (Circ J 2010; 74: 195 - 202).

Nifedipine improves endothelial function: role of endothelial progenitor cells.

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.