There are two local conditions for coronary artery spasmie. Firstly, coronary artery smooth muscle hyperresponsiveness that leads to coronary artery hypersensitive to vasoconstrictor substances results in increased contraction and even spasm and secondly, enough vasoconstrictor substances exists locally to induce coronary artery spasm. Endothelin-1 is the strongest vasoconstrictor substance in man. Studies have demonstrated that activation of extracellular signal-regulated kinases 1 and 2(ERK1/2)by risk factors for coronary spasm like hyperlipidemia and cigarette smoke can mediate endothelin receptor upregulation in coronary artery smooth muscle cells, subsequently results in significantly increased coronary artery sensitivity to endothelin-1 and leads to increase in vasoconstriction, and even vasospasm. Here, we review recent studies on the role of endothelin receptor upregulation in coronary artery spasm, which might provide new therapeutic targets and novel strategy for treatment of coronary artery spasm.