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Titolo:
Therapeutic potential of H-3-receptor agonists in myocardial infarction
Autore:
Mackins, CJ; Levi, R;
Indirizzi:
Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Dept Pharmacol, New York, NY 10021 USA
Titolo Testata:
EXPERT OPINION ON INVESTIGATIONAL DRUGS
fascicolo: 11, volume: 9, anno: 2000,
pagine: 2537 - 2542
SICI:
1354-3784(200011)9:11<2537:TPOHAI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
HISTAMINE H-3 RECEPTORS; NONEXOCYTOTIC NORADRENALINE RELEASE; MEDIATED NOREPINEPHRINE RELEASE; HUMAN CARDIAC TISSUE; PLATELET ACTIVATION; GUINEA-PIG; CELL-LINE; IN-VIVO; ISCHEMIA; MECHANISMS;
Keywords:
adrenergic; arrhythmias; cardioprotection; carrier-mediated; exocytosis; histamine H-3-receptors; myocardial infarction; myocardial ischaemia; Na+/H+ exchange; noradrenaline release; sympathetic nerve endings;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Levi, R Cornell Univ, Weill Med Coll, Dept Pharmacol, 1300 York Ave, New York, NY 10021 USA Cornell Univ 1300 York Ave New York NY USA 10021 ork, NY 10021 USA
Citazione:
C.J. Mackins e R. Levi, "Therapeutic potential of H-3-receptor agonists in myocardial infarction", EXPERT OP I, 9(11), 2000, pp. 2537-2542

Abstract

Sympathetic over-activity accompanied by excessive noradrenaline (NA) release within the heart is a recognised cause of dysfunction in myocardial ischaemia; Myocardial infarction is often accompanied by arrhythmias with highmorbidity and mortality. Indeed, NA enhances intracellular Ca2+ by increasing its influx through voltage-dependent channels, mobilising it from intracellular stores and favouring its inward transport by Na+/Ca2+ exchange. Ca2+ overload eventually results in dysrhythmia and uncoordinated myocyte contraction. Moreover, NA increases metabolic demand. In concert with other contributing factors, this will aggravate the primary ischaemia and initiate a vicious cycle;hat can culminate in myocardial damage and heart failure. Therefore, reduction of NA release from cardiac sympathetic nerves is an important protective measure. Adrenergic nerves possess inhibitory receptors, such as alpha (2)-adrenoceptors, adenosine A(1)-receptors and histamine H-3-receptors (H3R). In myocardial infarction, NA is released by both exocytotic (Ca2+-dependent) and carrier-mediated (Na+/H+ exchange-dependent) mechanisms, associated with short-term and protracted ischaemia, respectively. Unlike ar-adrenoceptor agonists that reduce NA exocytosis, but enhance carrier-mediated NA release, H3R agonists inhibit both exocytotic and carrier-mediated NA release. Moreover, unlike adenosine A(1)-receptor agonists, H3R agonists do not depress sinoatrial and atrioventricular nodes, nor cause bronchoconstriction. Therefore, stimulation of H3R on cardiac sympathetic nerveendings is an important new way to protect the heart from the consequencesof ischaemia and infarction, Although H3R agonists alleviate reperfusion arrhythmias in isolated hearts by reducing NA release, this protective action needs to be demonstrated in classical in vivo models of occlusion/reperfusion. Regardless, H3R agonists offer the promise of a novel strategy in thetreatment of myocardial ischaemia and infarction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 09:00:01