The role of Na⁺/H⁺exchanger in Ca²⁺overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice

• Main Authors: Anzawa Ryuko, Seki Shingo, Nagoshi Tomohisa, Taniguchi Ikuo, Feuvray Danielle, Yoshimura Michihiro
• Format: Article
• Language: English
• Published: BMC 2012-04-01
• Series: Cardiovascular Diabetology
• Online Access: http://www.cardiab.com/content/11/1/33
• ISSN: 1475-2840

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Hearts from male type 2 diabetic <it>db/db </it>(12-15 weeks old) and age-matched control <it>db/+ </it>mice were subjected to Langendorff perfusion and loaded with 4μM of the Ca²⁺indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca²⁺]_iwas measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured.</p> <p>Results</p> <p><it>db/db </it>hearts exhibited a lower recovery of LV developed pressure than <it>db/+ </it>hearts during reperfusion following ischemia. Diastolic [Ca²⁺]_iwas 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.</p> <p>Conclusion</p> <p>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 <it>db/db </it>mice.</p>