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Therefore, more therapeutic options specifically targeted to the DA should be considered. We hypothesized the DA possesses a unique genetic signature that would set it apart from other vessels. A microarray was used to compare the genetic profiles of the murine DA and ascending aorta (AO). Over 4,000 genes were differentially expressed between these vessels including a subset of ion channel-related genes. Specifically, the alpha and beta subunits of large-conductance calcium-activated potassium (BK<jats:sub>Ca<\/jats:sub>) channels are enriched in the DA. Gain- and loss-of-function studies showed inhibition of BK<jats:sub>Ca<\/jats:sub>channels caused the DA to constrict, while activation caused DA relaxation even in the presence of O<jats:sub>2<\/jats:sub>. This study identifies subsets of genes that are enriched in the DA that may be used to develop DA-specific drugs. Ion channels that regulate DA tone, including BK<jats:sub>Ca<\/jats:sub>channels, are promising targets. 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