Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
The myocardial Na+/H+ exchanger - A potential therapeutic target for the prevention of myocardial ischaemic and reperfusion injury and attenuation ofpostinfarction heart failure
Autore:
Karmazyn, M; Sostaric, JV; Gan, XT;
Indirizzi:
Univ Western Ontario, Dept Pharmacol & Toxicol, London, ON N6A 5C1, CanadaUniv Western Ontario London ON Canada N6A 5C1 London, ON N6A 5C1, Canada
Titolo Testata:
DRUGS
fascicolo: 3, volume: 61, anno: 2001,
pagine: 375 - 389
SICI:
0012-6667(2001)61:3<375:TMNE-A>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM-HYDROGEN EXCHANGE; PROTEIN-KINASE-C; NA-H EXCHANGE; INHIBITOR HOE-642 CARIPORIDE; ISOLATED RAT HEARTS; VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; INFARCT SIZE; SUBCELLULAR-LOCALIZATION; ANTIPORTER INHIBITORS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
91
Recensione:
Indirizzi per estratti:
Indirizzo: Karmazyn, M Univ Western Ontario, Dept Pharmacol & Toxicol, Med Sci Bldg, London, ON N6A 5C1, Canada Univ Western Ontario Med Sci Bldg London ON Canada N6A 5C1 ada
Citazione:
M. Karmazyn et al., "The myocardial Na+/H+ exchanger - A potential therapeutic target for the prevention of myocardial ischaemic and reperfusion injury and attenuation ofpostinfarction heart failure", DRUGS, 61(3), 2001, pp. 375-389

Abstract

The myocardial Na+/H+ exchange (NHE) represents a major mechanism for pH regulation during normal physiological processes but especially during ischaemia and early reperfusion. However, there is now very compelling evidence that its activation contributes to paradoxical induction of cell injury. The mechanism for this most probably reflects the fact that activation of theexchanger is closely coupled to Na+ influx and therefore to elevation in intracellular Ca2+ concentrations through the Na+/Ca2+ exchange. The NHE is exquisitely sensitive to intracellular acidosis; however, other factors canalso exhibit stimulatory effects vi a phosphorylation-dependent processes. The se generally represent various autocrine and paracrine as well as hormonal factors such as endothelin-1, angiotensin II and alpha (1)-adrenoceptor agonists, which probably act through receptor-signal transduction processes. Thus far, 6 NHE isoforms have been identified and designated as NHE1 through NHE6. All except NHE6, which is located intracellularly, are restricted to the sarcolemmal membrane. In the mammalian myocardium the NHE1 subtype is the predominant isoform, although NHE6 has also been identified in the heart. The predominance of NHE1 in the myocardium is of some importance since, as discussed in this review, pharmacological development of NHE inhibitors for cardiac therapeutics has concentrated specifically on those agents which are selective for NHE1. These agents, as well as the earlier nonspecific amiloride derivatives have now been extensively demonstrated to possess excellent cardioprotective properties, which appear to be superior to other strategies, including the extensively studied phenomenon of ischaemic preconditioning. Moreover, the salutary effects of NHE inhibitors have been demonstrated using a variety ofexperimental models as well as animal species suggesting that the role of the NHE in mediating injury is not species specific. The success of NHE inhibitors in experimental studies has led to clinical trials for the evaluation of these agents in high risk patients with coronary artery disease as well as in patients with acute myocardial infarction (MI). Recent evidence also suggests that NHE inhibition may be conducive to attenuating the remodelling process after MI, independently of infarct sizereduction, and attenuation of subsequent postinfarction heart failure. As such, inhibitors of NHE offer substantial promise for clinical development for attenuation of both acute responses to myocardial as well as chronic postinfarction responses resulting in the evolution to heart failure.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:02:35