Cardioprotective effect of an endothelin receptor antagonist during ischaemia/reperfusion in the severely atherosclerotic mouse heart.
Br J Pharmacol
; 144(6): 860-6, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15685207
ABSTRACT
1. Endothelin (ET) receptor antagonists are cardioprotective during myocardial ischaemia and reperfusion through a nitric oxide (NO)-dependent mechanism. The aim of the present study was to investigate whether the ET receptor antagonist, bosentan, is cardioprotective in atherosclerotic mice. 2. Buffer-perfused hearts from apolipoprotein E/LDL receptor double knockout (KO) and wild-type (WT) mice were subjected to global ischaemia and reperfusion. 3. Following reperfusion, the recovery of rate-pressure product (RPP; left ventricular developed pressure (LVDP) x heart rate) was equally impaired in WT and KO mice given vehicle (34+/-8 and 29+/-9%, respectively). The ET(A)/ET(B) receptor antagonist bosentan (10 micromol l(-1)) improved recoveries to 57+/-10% in WT and to 68+/-10% in KO mice (P<0.01). Similar effects were observed for the recovery of left ventricular end-diastolic pressure (LVEDP), developed pressure and dP/dt. 4. Bosentan improved the recovery of coronary flow in both KO and WT mice. Recovery of coronary flow was significantly higher in the KO mice given bosentan (135+/-15%) than in the WT group (111+/-12%; P<0.01). ET-1 (1 nmol l(-1)) impaired recovery of coronary flow in both WT and KO mice though this effect was more pronounced in the KO mice (P<0.01). 5. Coronary outflow of NO during reperfusion was enhanced in both KO and WT mice following bosentan administration. 6. The ET(A)/ET(B) receptor antagonist bosentan protects the atherosclerotic mouse heart from ischaemia/reperfusion injury. The observation that ET receptor blockade and stimulation have a greater effect on coronary flow in atherosclerotic hearts indicates an increased activation of the ET system in atherosclerotic coronary arteries.
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Base de dados:
MEDLINE
Assunto principal:
Arteriosclerose
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Cardiotônicos
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Traumatismo por Reperfusão Miocárdica
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Isquemia Miocárdica
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Antagonistas dos Receptores de Endotelina
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article