Endothelin receptor expression and pharmacology in human saphenous vein graft

We have investigated the expression and pharmacology of endothelin (ET) receptors in human aortocoronary saphenous vein grafts. Subtype‐selective ligands were used to autoradiographically identify ET A ([ 125 I]‐PD151242) and ET B ([ 125 I]‐BQ3020) receptors. In graft saphenous vein ET A receptors predominated in the media, with few ET B receptors identified. Neither subtype was detected in the thickened neointima. The ratio of medial ET A :ET B receptors was 75% : 25% in both graft and control saphenous vein. ET‐1 contracted control (EC 50 2.9 n M ) and graft (EC 50 4.5 n M ) saphenous vein more potently than diseased coronary artery (EC 50 25.5 n M ). In all three blood vessels ET‐1 was 100 times more potent than ET‐3 and three times more potent than sarafotoxin 6b (S6b). Little or no response was obtained in any vessel with the ET B agonist sarafotoxin 6c (S6c). The ET A antagonist PD156707 (100 n M ) blocked ET‐1 responses in all three vessels with p K b values of approximately 8.0. For individual graft veins the EC 50 value for ET‐1 and ‘age’ of graft in years showed a significant negative correlation. In conclusion there is no alteration in ET receptor expression in the media of saphenous veins grafted into the coronary circulation compared to control veins. ET A receptors predominantly mediate the vasoconstrictor response to ET‐1 in graft vein, with no apparent up‐regulation of ET B receptors. The sensitivity of the graft vein to ET‐1 increased with graft ‘age’, suggesting that these vessels may be particularly vulnerable to the increased plasma ET levels that are detected in patients with cardiovascular disease.British Journal of Pharmacology (1999) 126 , 443–450; doi: 10.1038/sj.bjp.0702326