Organic nitrates differentially modulate circulating endothelial progenitor cells and endothelial function in...

Symptomatic coronary artery disease (CAD) is usually treated with organic nitrates. Endothelial progenitor cells (EPCs) are a circulating cell population participating in vascular homeostasis in a nitric oxide-dependent manner. We investigated the effects of the nitric oxide donors isosorbide dinitrate (ISDN) and pentaerythritol tetranitrate (PETN) on EPC and endothelial function in patients with symptomatic CAD. We randomized 36 patients with angiographically proven CAD to treatment with either ISDN (40 mg retarded release orally two times per day; n = 18) or PETN (80 mg orally two times per day; n = 18) for 14 days (clinical trial number: NCT01030367). PETN treatment substantially increased numbers of circulating CD34(+)/KDR(+) EPCs (p = 0.02), whereas no effects were observed in patients treated with ISDN. EPC function assessed by formation of endothelial colonies was enhanced by twofold (p = 0.04) in patients treated with PETN. No changes were observed after ISDN treatment. Endothelial function, assessed by peripheral arterial tonometry, remained unchanged during PETN treatment, but was significantly impaired in patients treated with ISDN. Treatment of symptomatic CAD patients with PETN for 14 days significantly increased levels of circulating EPC and improved markers for EPC function, whereas ISDN was without effects on EPCs and worsened endothelial function.