2012年4月
The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice
CARDIOVASCULAR DIABETOLOGY
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- 巻
- 11
- 号
- 開始ページ
- 33
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1186/1475-2840-11-33
- 出版者・発行元
- BIOMED CENTRAL LTD
Background: A higher increase in intracellular Na+ via Na+/H+ exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE in inducing changes in cytoplasmic Ca2+ concentration ([Ca2+](i)) and alterations in ventricular function during ischemia-reperfusion in type 2 diabetic mouse hearts.
Methods: Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 mu M of the Ca2+ indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca2+](i) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured. Results: db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic [Ca2+](i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca2+ overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure.
Conclusion: NHE plays a key role in enhancing cytoplasmic Ca2+ overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
Methods: Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 mu M of the Ca2+ indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca2+](i) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured. Results: db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic [Ca2+](i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca2+ overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure.
Conclusion: NHE plays a key role in enhancing cytoplasmic Ca2+ overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
- リンク情報
- ID情報
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- DOI : 10.1186/1475-2840-11-33
- ISSN : 1475-2840
- eISSN : 1475-2840
- PubMed ID : 22490613
- Web of Science ID : WOS:000304865000001