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.
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Authors | Kenzo Takahashi, Teisuke Takahashi, Taizo Suzuki, Michihito Onishi, Yu Tanaka, Akiko Hamano-Takahashi, Tomomi Ota, Kazuya Kameo, Toshio Matsuda, Akemichi Baba |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 458
Issue 1-2
Pg. 155-62
(Jan 01 2003)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 12498920
(Publication Type: Journal Article)
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Chemical References |
- 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
- Aniline Compounds
- Anti-Arrhythmia Agents
- Guanidines
- Phenyl Ethers
- SEA 0400
- Sodium-Calcium Exchanger
- Sulfones
- cariporide
- Thiourea
- Calcium
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Topics |
- Aniline Compounds
(pharmacology)
- Animals
- Anti-Arrhythmia Agents
(pharmacology)
- Arrhythmias, Cardiac
(physiopathology, prevention & control)
- Calcium
(metabolism, pharmacokinetics)
- Cell Survival
(drug effects)
- Cells, Cultured
- Dogs
- Guanidines
(pharmacology)
- Heart
(drug effects, physiopathology)
- In Vitro Techniques
- Male
- Myocardial Reperfusion Injury
(physiopathology, prevention & control)
- Myocardium
(metabolism)
- Myocytes, Cardiac
(cytology, drug effects, metabolism)
- Phenyl Ethers
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Rats, Wistar
- Sarcolemma
(drug effects, metabolism)
- Sodium-Calcium Exchanger
(antagonists & inhibitors, metabolism)
- Sulfones
(pharmacology)
- Thiourea
(analogs & derivatives, pharmacology)
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