© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury
aGlaxoSmithKline Laboratoires Pharmaceutiques, 4 Rue du Chesnay-Beauregard, BP 96205, 35762 Saint-Grégoire Cédex, France
bDepartment of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
nassirah_khandoudi{at}sbphrd.com
* Corresponding author. Tel.: +33-2-9928-0461; fax: +33-2-9928-0444
Objective: Although it is believed that sodium-driven acid–base transport plays a central role in the development of the reperfusion injury that follows cardiac ischemia, research to date has demonstrated only a role for Na+/H+ exchange (NHE). However, Na+-driven HCO–3 transport, which is quantitatively as important as NHE in cardiac cells, has not been examined. Methods and Results: Here the results show that a neutralizing antibody raised against the human heart electrogenic Na+/HCO3– cotransporter (hhNBC) blocked the recovery of pH after acidic pulse both in HEK-293 cells expressing hhNBC and in rat cardiac myocytes demonstrating the presence of an electrogenic NBC in rat cardiac myocytes similar to hhNBC. Administration of anti-NBC antibody to ischemic-reperfused rat hearts markedly protects systolic and diastolic functions of the heart during reperfusion. Furthermore, using a quantitative real-time RT-PCR (TaqMan) and Western blot analysis we demonstrated that in human cardiomyopathic hearts, mRNA and protein levels of hhNBC increase, whereas mRNA levels of the electroneutral Na+/HCO3– cotransporter (NBCn1) remain unchanged. Conclusion: Our data provide evidence that inhibition of hhNBC, whose role in cardiac pathologies could be amplified by overexpression, represents a novel therapeutic approach for ischemic heart disease.
KEYWORDS Cardiomyopathy; Gene expression; Ion transport; Ischemia; Reperfusion; Ventricular function
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