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Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger, on myocardial ischemia-reperfusion injuries
- Source :
- European journal of pharmacology. 458(1-2)
- Publication Year :
- 2002
-
Abstract
- The Na(+)/Ca(2+) exchanger (NCX) is involved in myocardial ischemia-reperfusion injuries. We examined the effects of 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a potent and selective inhibitor of NCX, on myocardial ischemia-reperfusion injury models. In canine cardiac sarcolemmal vesicles and rat cardiomyocytes, SEA0400 potently inhibited the Na(+)-dependent 45Ca(2+) uptake with an IC(50) value of 90 and 92 nM, compared with 2-[2-[4-(4-nitrobenzyloxy)phenyl]isothiourea (KB-R7943, 7.0 and 9.5 microM), respectively. In rat cardiomyocytes, SEA0400 (1 and 3 microM) attenuated the Ca(2+) paradox-induced cell death. In isolated rat Langendorff hearts, SEA0400 (0.3 and 1 microM) improved the cardiac dysfunction induced by low-pressure perfusion followed by normal perfusion. In anesthetized rats, SEA0400 (0.3 and 1 mg/kg, i.v.) reduced the incidence of ventricular fibrillation and mortality induced by occlusion of the left anterior descending coronary artery followed by reperfusion. These results suggest that SEA0400 is a most potent NCX inhibitor in the heart and that it has protective effects against myocardial ischemia-reperfusion injuries.
- Subjects :
- Male
medicine.medical_specialty
Cell Survival
Ischemia
Myocardial Reperfusion Injury
Pharmacology
In Vitro Techniques
Guanidines
Sodium-Calcium Exchanger
Rats, Sprague-Dawley
Dogs
Sarcolemma
In vivo
Internal medicine
medicine
Myocyte
Animals
Myocytes, Cardiac
Sulfones
Rats, Wistar
Cells, Cultured
Aniline Compounds
biology
business.industry
Myocardium
Phenyl Ethers
Fissipedia
Thiourea
Arrhythmias, Cardiac
Heart
biology.organism_classification
medicine.disease
Rats
Mechanism of action
Circulatory system
Ventricular fibrillation
Cardiology
Calcium
medicine.symptom
business
Perfusion
Anti-Arrhythmia Agents
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 458
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....5d0939e52b7738da651b482e5397bef5