Linked Life Data

9421282

Source:http://linkedlifedata.com/resource/pubmed/id/9421282

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1998-2-5
pubmed:abstractText
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 prevented APD prolongation caused by OFR (137+/-12 ms after DHF vs 117+/-6 ms before DHF n=14, not significant) but not the decrease of MDP (-63.4+/-2.5 mV after DHF vs -70.9+/-1.0 mV before DHF, P<0.05). 5. The e.s.r. spectra obtained from the DHF-DMPO solution in the absence of darodipine demonstrated the presence of two components corresponding to two DMPO adducts. The addition of darodipine (50-500 nM) led to a concentration-dependent decrease in intensity of the signals, the intensity of the DMPO-COO.- adduct being decreased more than that of the DMPO-OH. adduct. 6. Our results demonstrate that darodipine dose-depentently blocks I(Ca,L) in rat isolated cardiomyocytes. Furthermore it exerts protective effects against free-radical-induced electrophysiological alterations independently of its calcium antagonistic properties; this effect is possibly due to trapping of specific radical species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0007-1188
pubmed:author
pubmed:issnType
Print
pubmed:volume
122
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1353-60
pubmed:dateRevised
2008-11-20
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical-mediated injury.
pubmed:affiliation
Department of Pharmacology, University of Firenze, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't