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

Abstract

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 Ca(2+) concentration ([Ca(2+)](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 μM of the Ca(2+) indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca(2+)](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 [Ca(2+)](i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca(2+) 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 Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.

• Authors: Ryuko Anzawa, Shingo Seki, Tomohisa Nagoshi, Ikuo Taniguchi, Danielle Feuvray, Michihiro Yoshimura
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 11 Pg. 33 (Apr 11 2012) ISSN: 1475-2840 [Electronic] England
• PMID: 22490613 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Diabetes Mellitus, Type 2 (physiopathology)
• Disease Models, Animal
• Guanidines (pharmacology)
• Male
• Mice
• Mice, Mutant Strains
• Myocardial Reperfusion Injury (physiopathology)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, drug effects, physiology)
• Sulfones (pharmacology)
• Ventricular Dysfunction, Left (physiopathology)