Endothelins are very potent vasoconstrictors that bind to smooth muscle endothelin receptors (GPCR-A7 subfamily), of which there are two subtypes: ETA and ETB receptors. Their activation causes the release of calcium by the sarcoplasmic reticulum (SR) and increased smooth muscle contraction and vasoconstriction. The receptors have been implicated in the pathogenesis of hypertension, coronary vasospasm, and heart failure.