Comparative effects of different dihydropyridines on the expression of adhesion molecules induced by TNF-alpha on endothelial cells

Objective Lacidipine has already been demonstrated to reduce the expression of some adhesion molecules induced by pro-oxidant signals on endothelial c ells. In order to verify if this effect is a peculiarity of this molecule, or belongs to other dihydropyridinic compounds (DHPs), the activity of laci dipine was compared with that of lercanidipine, amlodipine, nimodipine and nifedipine. Design and methods The compounds were incorporated in human umbilical vein endothelial cells (HUVECs) using native low-density lipoprotein as a carrie r. The drug concentrations in HUVECs were measured by mass spectrometry. Hu man recombinant tumour necrosis factor-alpha was then incubated with HUVECs for 7 h at 37 degrees C for adhesion molecule expression. Results The cellular amount of lacidipine, lercanidipine and amlodipine was similar, while nimodipine and nifedipine were almost undetectable or undet ectable, respectively. Lacidipine, at any concentration, determined a dose- dependent significant decrease of the expression of intercellular adhesion molecule-1 (ICAM-1) ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) VCAM -1 and E-selectin (P < 0.01), Lercanidipine and amlodipine determined varia ble decreases of adhesion molecules at the intermediate and highest concent rations. Nimodipine and nifedipine determined no effect on ICAM-1,VCAM-1 an d E-selectin. The lowest IC50, i.e. the concentration determining the 50% r eduction of ICAM-1, VCAM-1 and E-selectin expression was obtained with laci dipine for all the adhesion molecules considered (P < 0.01), Conclusions It is concluded that the effect of the DHPs used in this study on adhesion molecule expression is determined first by their lipophilicity and then by their intrinsic antioxidant activity. J Hypertens 1999, 17:1837 -1841 (C) Lippincott Williams & Wilkins.