NO-synthase inhibitors provide influence on protective effect of modified endotoxine diphosphoryl lipid A in a rat heart model of ischemic-reperfusion injury.

Abstract

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.

• Authors: M Kuzelová, M Mladonická, M Bukovský, M Dubnicková, A Adameová, P Svec
• Journal: Die Pharmazie (Pharmazie) Vol. 61 Issue 6 Pg. 568-70 (Jun 2006) ISSN: 0031-7144 [Print] Germany
• PMID: 16826982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Enzyme Inhibitors
• Lipid A
• diphosphoryl lipid A
• Isothiuronium
• Nitric Oxide Synthase Type II
• S-methylisothiopseudouronium
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Enzyme Inhibitors (pharmacology)
• In Vitro Techniques
• Isothiuronium (analogs & derivatives, pharmacology)
• Lipid A (analogs & derivatives, pharmacology)
• Male
• Myocardial Reperfusion Injury (pathology, prevention & control)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Rats
• Rats, Wistar
• Tachycardia (drug therapy, physiopathology)