Compositions and methods for treating hypertension in a subject are provided, including administering an antisense oligomer effective to reduce expression of cytochrome P450 3A5 (CYP3A5) enzyme. The antisense oligomer includes phosphorodiamidate morpholino oligonucleotide (PMO), phosphorothioate 2′;-O-methyl oligoribonucleotides (PSO), locked nucleic acid nucleotide, locked nucleic acid analog nucleotide, or another modified oligonucleotide backbone or nuclease-resistant backbone. The antisense oligomer is administered transdermally, subcutaneously, or orally, and optionally with a pharmaceutically acceptable carrier. In one embodiment, the antisense oligomer is an oligomer that is antisense to mRNAs that encode CYP3A5, for instance targeted at the AUG start site of the mRNAs that encode CYP3A5 or at a G4 structure within CYP3A5.