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Titolo:
EFFECTS OF THE ET(A) ET(B) RECEPTOR ANTAGONIST, BOSENTAN ON ENDOTHELIN-1-INDUCED MYOCARDIAL-ISCHEMIA AND EDEMA IN THE RAT/
Autore:
FILEP JG; FOURNIER A; FOLDESFILEP E;
Indirizzi:
UNIV MONTREAL,MAISONNEUVE ROSEMONT HOSP,RES CTR MONTREAL PQ H1T 2M4 CANADA INST NATL RECH SCI SANTE POINTE CLAIRE PQ H9R 1G6 CANADA
Titolo Testata:
British Journal of Pharmacology
fascicolo: 2, volume: 116, anno: 1995,
pagine: 1745 - 1750
SICI:
0007-1188(1995)116:2<1745:EOTEER>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
ETA RECEPTOR; AGONIST; POTENT; VASOCONSTRICTOR; VASODILATION; PERMEABILITY; FR139317; SUBTYPES; IRL-1620; CLONING;
Keywords:
ENDOTHELIN; ET(A) AND ET(B) RECEPTORS; BOSENTAN; IRL 1620; MYOCARDIAL ISCHEMIA; VASCULAR PERMEABILITY; RAT HEART;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
J.G. Filep et al., "EFFECTS OF THE ET(A) ET(B) RECEPTOR ANTAGONIST, BOSENTAN ON ENDOTHELIN-1-INDUCED MYOCARDIAL-ISCHEMIA AND EDEMA IN THE RAT/", British Journal of Pharmacology, 116(2), 1995, pp. 1745-1750

Abstract

1 The purposes of this study were to assess the role of ET(B) receptors in mediating endothelin-l (ET-1)-induced myocardial ischaemia and oedema in rats and to study the inhibitory action of the novel nonpeptide ET(A)/ET(B) receptor antagonist, bosentan on these actions of ET-1.2 Intravenous bolus injection of ET-1 (1 nmol kg(-1)) into anaesthetized rats produced marked ST segment elevation of the electrocardiogramwithout causing arrhythmias. ST segment elevation developed within 30-50 s and persisted for at least 30 min following injection of the peptide. 3 Pretreatment of the animals with bosentan (10 mg kg(-1), i.v.)inhibited on average by 96% the ST segment elevation elicited by ET-1(I nmol kg(-1)) compared to the 82% inhibition observed with the ET(A) receptor-selective antagonist, FR 139317 (2.5 mg kg(-1), i.v.). 4 Bolus injection of ET-1 (1 nmol kg(-1), i.v.) to conscious chronically catheterized rats evoked a transient depressor response followed by a prolonged presser effect. Corresponding to changes in blood pressure, atransient tachycardia and a sustained bradycardia were observed. ET-1(1 nmol kg(-1)) enhanced albumin extravasation by 119 and 93% in the left ventricle and right atrium, respectively, as measured by the local extravascular accumulation of Evans blue dye. 5 Pretreatment of the animals with bosentan (10 mg kg(-1)) inhibited by 71 and 90% the depressor and presser actions of ET-1 (1 nmol kg(-1)) and the accompanying tachycardia and bradycardia, respectively. FR 139317 (2.5 mg kg(-1)) attenuated the presser response to ET-I and accompanying bradycardia by75%, without affecting the depressor action and accompanying tachycardia. ET-l-induced albumin extravasation was completely inhibited by bosentan (10 mg kg(-1)) both in the left ventricle and right atrium, compared to the 86% inhibition observed with FR 139317 (2.5 mg kg(-1)). 6Like ET-1, the ET(B) receptor-selective agonist, IRL 1620 (0.3 and 1 nnol kg(-1), i.v.) also produced dose-dependent ST segment elevation in anaesthetized rats and enhanced albumin extravasation (up to 141% ofcontrol) in the left ventricle and right atrium, respectively, in conscious rats. These effects of IRL 1620 were completely prevented by bosentan (10 mg kg(-1)). 7 These results indicate that ET(B) receptors, albeit to a lesser extent than ET(A) receptors, are also involved in mediating ET-l-induced myocardial ischaemia and oedema in the rat, and suggest the therapeutic potential for bosentan in the treatment of ischaemic myocardial diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:36:25