Down-regulation of endothelin B receptors in autogenous saphenous veins grafted into the arterial circulation.

Abstract

It has been postulated that endothelin (ET) might be involved in the development of atherosclerotic vascular lesions. The present study was done to characterize changes in the contractility and ET receptor subtypes in the autogenous saphenous vein graft (VG). The rabbit saphenous vein (SV) was grafted into the ipsilateral femoral artery (FA), and at 4 weeks after the operation, VG was harvested. In the medial layer samples of SV, VG and FA, the cytosolic Ca2+ concentration ([Ca2+]i) and force were monitored using front-surface fluorometry of fura-PE3, and mRNA expression of ET receptors was evaluated using the reverse transcription polymerase chain reaction. ET-1 (10(-7) M) developed force in SV, VG and FA, to the same extent. Sarafotoxin (S6c; 10(-7) M) developed force in the SV to the same extent as ET-1. However, S6c did not develop force in FA, and slight force developed in VG. Contractions induced by ET-1 were associated with increases in [Ca2+]i. FA expressed ETA receptor mRNA predominantly, and SV expressed both ETA and ETB receptors mRNAs. In VG, the expression of ETB receptor mRNA was markedly reduced, but expression of ETA receptor mRNA remained unchanged. Functioning ETB receptors and their mRNA are down-regulated when veins are grafted into the arterial circulation. All these changes in gene expression and function are part of adaptive responses known as 'arterialization'.