NO-synthase inhibitors provide influence on protective effect of modified endotoxine diphosphoryl lipid A in a rat heart model of ischemic-reperfusion injury.
The present study was designed to assess whether a protective effect of the modified diphosphoryl lipid A (modLA) against myocardial ischemia-reperfusion injury (IRI) in rats can be related to the mechanism involving inducible nitric oxide synthase (iNOS). Pre-treatment with modLA significantly reduced the duration of both ventricular tachycardia (p < 0.01) and ventricular fibrillation (p < 0.001) compared to controls. Under these conditions the incidence of animal death was reduced (p < 0.05). The beneficial effect of modLA was markedly attenuated by the prior administration of selective iNOS inhibitor S-methylisothiourea (SMT). In this animal group, mortality was significantly increased (p < 0.01) partially in consequence of sustained ventricular arrhythmias. These results indicate that induction of iNOS can be responsible for cardioprotection of modLA.
Kuzelová
M
M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic. kuzelova@fpharm.uniba.sk
Mladonická
M
M
Bukovský
M
M
Dubnicková
M
M
Adameová
A
A
Svec
P
P
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013610:Tachycardia / Q000188:drug therapy / Q000503:physiopathology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D008050:Lipid A; C049596:diphosphoryl lipid A; D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium; D019331:NG-Nitroarginine Methyl Ester