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001-es BibID:	BIBFORM030261
035-os BibID:	(Scopus)0141540407 (WoS)000184795700023
Első szerző:	Kovács Anikó
Cím:	Beta-adrenoceptor activation plays a role in the reverse rate-dependency of effective refractory period lengthening by dofetilide in the guinea-pig atrium, in vitro / Anikó Kovács, János Magyar, Tamás Bányász, Péter P. Nánási, Gábor Szénási
Dátum:	2003
ISSN:	0007-1188
Megjegyzések:	1 Blockers of the rapid component of the delayed rectifier potassium current (I-Kr) prolong cardiac action potential duration (APD) and effective refractory period (ERP) in a reverse rate-dependent manner. Since activation of beta-adrenoceptors attenuates prolongation of APD evoked by I-Kr blockers, rate-dependent neuronal noradrenaline liberation in the myocardium may contribute to the reverse rate-dependent nature of the effects of I-Kr blockers. In order to test this hypothesis, we studied the effects of dofetilide, a pure I-Kr blocker, on ERP after activation or blockade of beta-adrenoceptors and after catecholamine depletion in guinea-pig left atrial myocardium paced at 3, 2 and 1 Hz, in vitro. 2 Dofetilide (100 nM) lengthened ERP in a reverse rate-dependent manner in the left atrial myocardium of guinea-pigs. Strong activation of beta-adrenoceptors using 10 nM isoproterenol abolished the dofetilide-induced lengthening of ERP at all pacing rates. 3 Blockade of the beta-adrenoceptors with metoprolol (1 muM), atenolol (3 muM) or propranolol (300 nM) increased the dofetilide-evoked prolongation of ERP at 3 and 2 Hz, but not at 1 Hz. As a consequence, metoprolol attenuated while propranolol and atenolol fully eliminated the reverse rate-dependent nature of the dofetilide-induced ERP lengthening. In catecholamine-depleted atrial preparations of the guinea-pig (24 h pretreatment with 5 mg kg(-1) reserpine i.p.), the effect of dofetilide on ERP was not frequency dependent, and propranolol did not alter the effects of dofetilide. 4 In contrast to results obtained in guinea-pig atrial preparations, propranolol failed to change the reverse rate-dependent effect of dofetilide on ERP in the right ventricular papillary muscles of rabbits and guinea-pigs. 5 As an indication of the functional consequences of rate-dependent noradrenaline liberation, propranolol decreased twitch tension at 3 and 2 Hz but not at 1 Hz in the atrial myocardium of control guinea-pigs, whereas no such effect was detected in catecholamine-depleted atrial preparations. Propranolol failed to change contractility of ventricular myocardium in guinea-pigs and rabbits. 6 It is concluded that rate-dependent noradrenaline release and the ensuing beta-adrenoceptor activation contributed to the reverse rate-dependent nature of ERP prolongation caused by I-Kr blockers in isolated guinea-pig atrial myocardium.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	British Journal of Pharmacology. - 139 : 8 (2003), p. 1555-1563. -
További szerzők:	Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Szénási Gábor
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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