Endothelium-dependent and Independent Responsiveness to Endothelin in Porcine Coronary Artery

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the mechanism of endothelium-dependent and independent responses to endothelins (ETs) in porcine coronary artery. METHODS: The vascular rings of left anterior descending artery or left circumflex artery from 7 pigs were suspended in conventional organ chambers for the measurement of isometric force. To evaluate relaxation responses, vascular rings with endothelium were exposed to ET-1 and ET-3. To evaluate contraction responses, vascular rings with and without endothelium were exposed to ET-1 and ET-3 in the presence or absence of BQ 123 (ET(A) receptor antagonist) or TAK-044 (ET(A) and ET(B) receptor antagonist). RESULTS: Transient relaxation responses of vascular rings occurred after exposure of ET-1 and ET-3. These transient responses disappeared after preincubation with N-nitro-L arginine. There was an increased contractions of vascular rings according to increasing concentration of ET-1 and ET-3. The initial responses were enhanced in vascular rings without endothelium in ET-1 and ET-3. In vascular rings with endothelium, the contraction responses were more reduced in vascular rings with preincubation of BQ 123 than in vascular rings without BQ 123 in ET-1. In vascular rings without endothelium, the contraction responses were more reduced in vascular rings with preincubation of TAK-044 than in vascular rings without TAK-044 in ET-1. CONCLUSION: ET(B) receptor on the endothelium might mediate the transient vasodilator responses to ET-1 and ET-3 through release of nitric oxide in porcine coronary artery. ET(A) and ET(B) receptor on vascular smooth muscle cells might mediate vasoconstrictor responses to ETs.