PDE4D and hypertensive disorder: To explore whether PDE4D, via SMCs or ECs, plays a role in hypertension, we generated Pde4d SMC-specific knockout mice (Tagln-Cre mice; Pde4dSMC−/−) and Pde4d EC-specific knockout mice (Tek-Cre mice; Pde4dEC−/−) mice via Cre-LoxP recombinase system, and confirmed the mice genotypes by agarose gel electrophoresis genotyping and western blot (Supplementary Fig. 3a–e).