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

<p>Abstract</p> <p>Background</p> <p>A higher increase in intracellular Na<sup>+ </sup>via Na<sup>+</sup>/H<sup>+ </sup>exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE...

Full description

Bibliographic Details
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
_version_ 1818210981987221504
author Anzawa Ryuko
Seki Shingo
Nagoshi Tomohisa
Taniguchi Ikuo
Feuvray Danielle
Yoshimura Michihiro
author_facet Anzawa Ryuko
Seki Shingo
Nagoshi Tomohisa
Taniguchi Ikuo
Feuvray Danielle
Yoshimura Michihiro
author_sort Anzawa Ryuko
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>A higher increase in intracellular Na<sup>+ </sup>via Na<sup>+</sup>/H<sup>+ </sup>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<sup>2+ </sup>concentration ([Ca<sup>2+</sup>]<sub>i</sub>) 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 Ca<sup>2+ </sup>indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca<sup>2+</sup>]<sub>i </sub>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.</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 [Ca<sup>2+</sup>]<sub>i </sub>was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca<sup>2+ </sup>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 Ca<sup>2+ </sup>overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic <it>db/db </it>mice.</p>
first_indexed 2024-12-12T05:25:15Z
format Article
id doaj.art-fc7eb2b3ed2c45e9b49137056d91e9f0
institution Directory Open Access Journal
issn 1475-2840
language English
last_indexed 2024-12-12T05:25:15Z
publishDate 2012-04-01
publisher BMC
record_format Article
series Cardiovascular Diabetology
spelling doaj.art-fc7eb2b3ed2c45e9b49137056d91e9f02022-12-22T00:36:30ZengBMCCardiovascular Diabetology1475-28402012-04-011113310.1186/1475-2840-11-33The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>miceAnzawa RyukoSeki ShingoNagoshi TomohisaTaniguchi IkuoFeuvray DanielleYoshimura Michihiro<p>Abstract</p> <p>Background</p> <p>A higher increase in intracellular Na<sup>+ </sup>via Na<sup>+</sup>/H<sup>+ </sup>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<sup>2+ </sup>concentration ([Ca<sup>2+</sup>]<sub>i</sub>) 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 Ca<sup>2+ </sup>indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca<sup>2+</sup>]<sub>i </sub>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.</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 [Ca<sup>2+</sup>]<sub>i </sub>was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca<sup>2+ </sup>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 Ca<sup>2+ </sup>overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic <it>db/db </it>mice.</p>http://www.cardiab.com/content/11/1/33
spellingShingle Anzawa Ryuko
Seki Shingo
Nagoshi Tomohisa
Taniguchi Ikuo
Feuvray Danielle
Yoshimura Michihiro
The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
Cardiovascular Diabetology
title The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
title_full The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
title_fullStr The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
title_full_unstemmed The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
title_short The role of Na<sup>+</sup>/H<sup>+ </sup>exchanger in Ca<sup>2+ </sup>overload and ischemic myocardial damage in hearts from type 2 diabetic <it>db/db </it>mice
title_sort role of na sup sup h sup sup exchanger in ca sup 2 sup overload and ischemic myocardial damage in hearts from type 2 diabetic it db db it mice
url http://www.cardiab.com/content/11/1/33
work_keys_str_mv AT anzawaryuko theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT sekishingo theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT nagoshitomohisa theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT taniguchiikuo theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT feuvraydanielle theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT yoshimuramichihiro theroleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT anzawaryuko roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT sekishingo roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT nagoshitomohisa roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT taniguchiikuo roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT feuvraydanielle roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice
AT yoshimuramichihiro roleofnasupsuphsupsupexchangerincasup2supoverloadandischemicmyocardialdamageinheartsfromtype2diabeticitdbdbitmice