Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical-mediated injury

British Journal of Pharmacology
R MatucciA Mugelli

Abstract

1. We used electrophysiological and electron spin resonance (e.s.r.) techniques to study the mechanism of the protective effect of darodipine on rat isolated cardiomyocytes exposed to an exogenous source of oxygen free radicals (OFR). 2. The L-type calcium current (I(Ca,L)), action potential and cell shortening were measured in patch-clamped cells in the whole-cell configuration. I(Ca,L) blockade by darodipine was concentration-dependent, peak current being reduced by 20% with 50 nM and by 58% with 100 nM darodipine. The lowest concentration of darodipine did not affect action potential or twitch profile. 3. Exposure to OFR-generating solution (5 mM dihydroxyfumarate, DHF) caused the appearance of electrophysiological alterations and/or spontaneous activity in 73% of cells (n=26) within 5 min; action potential duration (APD) was prolonged (195+/-16 ms vs 140+/-6 ms in the control) and maximum diastolic potential (MDP) was reduced (-59.5+/-2.6 mV vs -69.8+/-0.8 mV in the control) (P<0.05, n=25). 4. A 2 min pretreatment with 50 nM darodipine significantly reduced the incidence of these arrhythmogenic events following a 5 min exposure to OFR (36% of cells, n=14; P<0.05 vs nonpretreated cells). Pretreatment with darodipine also pre...Continue Reading

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Citations

Aug 6, 1999·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·A A De Artinano, V L Gonzalez
Aug 30, 2008·Journal of Medicinal Chemistry·Emanuele CarosatiGabriele Cruciani
Aug 18, 2006·Journal of Medicinal Chemistry·Emanuele CarosatiFrank J Devlin

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