title: [Simvastatin and ischemia-reperfusion damage: its effects on apoptotic myocyte death and on the endothelial expression of nitric-oxide synthetase in an experimental model of the isolated rat heart].
abstract: Recent studies have suggested that simvastatin may exert endothelial-protective and anti-ischemic effects via nitric oxide (NO) mechanisms. The aim of this study was to evaluate, in isolated working rat hearts, the effect of acute simvastatin administration on endothelial and inducible NO-synthase (eNOS and iNOS) mRNA and on myocytic apoptosis after ischemia-reperfusion. We used isolated working rat hearts submitted to 15 min global, no-flow, normothermic ischemia and 180 min reperfusion. To detect myocytic apoptosis we used DNA agarose gel electrophoresis and Tunel technique; eNOS and iNOS expression were evaluated by multiplex reverse transcriptase-polymerase chain reaction; glyceraldehyde-3-phosphate dehydrogenase (G3PDH) was used as standard. The eNOS and iNOS mRNAs were expressed as G3PDH/eNOS and G3PDH/iNOS densitometric ratio (BioRad Gel Doc 1000). Hearts were divided into four groups: A) hearts excised and used as histological controls; B) untreated hearts submitted to ischemia and reperfusion; C) actinomicin D-treated (1.5 mg/kg) hearts, perfused with 25 microM simvastatin, subjected to ischemia and reperfusion; D) hearts treated with simvastatin 25 microM and submitted to ischemia and reperfusion. In Group B we evidenced a significant myocytic apoptotic damage, reduced in groups C and D. In Group B an increase in G3PDH/eNOS ratio vs Group A was detected; in Group D a reduction in G3PDH/eNOS ratio vs Group B occurred; no significant changes were observed between groups C and D. As for G3PDH/iNOS ratio, it was significantly increased in Group D with respect to groups A and B. Our data suggest that simvastatin in acute may modulate NO-synthase mRNA expression (induction of eNOS mRNA by means of post-transcriptional mechanisms and inhibition of iNOS postischemic overexpression) and reduce myocytic apoptosis.
authors: Dipartimento di Scienze Cliniche e di Bioimmagini, Università degli Studi G. D'Annunzio, Chieti.
authors: P
authors: P
authors: Di Napoli
authors: A
authors: A
authors: Maggi
authors: R
authors: R
authors: Spina
authors: L
authors: L
authors: Barsotti
authors: A A
authors: AA
authors: Taccardi
authors: L
authors: L
authors: Stuppia
authors: G
authors: G
authors: Vianale
authors: G
authors: G
authors: Palka
authors: A
authors: A
authors: Barsotti
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006321:Heart / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D019001:Nitric Oxide Synthase