© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
The Na–H exchanger revisited: an update on Na–H exchange regulation and the role of the exchanger in hypertension and cardiac function in health and disease
aDepartment of Physiology, Emory University School of Medicine, Atlanta, GA 30322, USA
bDepartment of Pharmacology and Toxicology, University of Western Ontario, Medical Sciences Building, London, Ontario, Canada N6A 5C1
* Corresponding author. Tel.: (+1-519) 6613872; Fax: (+1-519) 6614051; E-mail: mkarm@julian.uwo.ca
Received 23 June 1997; accepted 31 July 1997
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1 Introduction |
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The Spotlight Issue of Cardiovascular Research, published in early 1995, was dedicated to various aspects of the Na–H exchanger (NHE) as they pertain to the cardiovascular system. It is appropriate to state that since the publication of that issue major strides have occurred which serve to enhance our understanding and appreciation of the importance of this major pH regulatory process in the cardiovascular system, both with respect to normal homeostasis as well as pathology. This brief revue has been written in order to provide an ‘update’ on developments in this active field since the publication of the Cardiovascular Research Spotlight Issue, again with a focus on the cardiovascular system in health and disease. The review is not intended as an exhaustive treatment of this topic, but rather it concentrates on recent developments and, accordingly, the authors have relied primarily on publications which have appeared in 1994 and later, except
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2 NHE isoforms |
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3 Regulation of NHE function |
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3.1 Intracellular signalling intermediates involved in NHE-1 regulation
3.2 Transcriptional regulation of NHE-1
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4 Role of NHE in hypertension |
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5 Role of NHE in regulation of cardiac function |
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6 Cardioprotective effect of NHE inhibition |
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6.1 Studies with amiloride analogues
6.2 Studies with HOE 694 and HOE 642 (cariporide)
6.3 Interaction between NHE inhibitors and other cardioprotective agents
6.4 NHE inhibition and cardiac protection during prolonged hypothermic storage
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7 Mechanism of NHE involvement in cardiac injury |
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7.1 Role of NHE in mediating toxic effects of ischemic metabolites
7.2 NHE and apoptosis
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8 Role of NHE in postinfarction responses |
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9 Intracellular pH and potential role of NHE in ischemic preconditioning |
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10 Clinical evaluation of HOE 642 (cariporide) in high risk cardiac patients |
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11 Role of NHE in other forms of the diseased myocardium? |
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11.1 NHE in diabetic heart
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12 Conclusions |
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