In the early stages of hypertension in the SHR, the heightened sympathetic responsiveness may result from down-regulation of M-current that restricts neural firing (Davis et al., 2020), local inflammation associated with macrophages (Neely et al., 2022), increased activity of Cav2.2 (Larsen et al., 2016a), impaired NO-cGMP signaling (Li et al., 2007), and abnormal regulation of mitochondrial phosphodiesterases (Li et al., 2022). The gene discussed is CACNA1B; the disease is Hypertension.