title: The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved?
abstract: Atherosclerosis results from multiple factors and involves several mechanisms, including endothelial monocyte and smooth muscle cell (SMC) changes, cholesterol accumulation, plaque rupture and thromboembolism. Calcium ions play a role in the initial and chronic development of atherosclerotic lesions. Several studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. In this study the antiatherogenic activity of lercanidipine, a new lipophilic, second-generation calcium antagonist, was investigated. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentrations ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC, with the (S)-enantiomer (69% inhibition) being 2.4-fold more active than the (R)-counterpart (29% inhibition). The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm, at least in vitro, the pharmacological potential of the compound to influence negatively the process of atherogenesis.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corsini
authors.forename: M R
authors.initials: MR
authors.lastname: Accomazzo
authors.forename: M
authors.initials: M
authors.lastname: Canavesi
authors.forename: A
authors.initials: A
authors.lastname: Sartani
authors.forename: R
authors.initials: R
authors.lastname: Testa
authors.forename: A L
authors.initials: AL
authors.lastname: Catapano
authors.forename: R
authors.initials: R
authors.lastname: Fumagalli
authors.forename: R
authors.initials: R
authors.lastname: Paoletti
authors.forename: F
authors.initials: F
authors.lastname: Bernini
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009568:Nitrendipine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009568:Nitrendipine; C060343:lercanidipine