title: [WNK-SPAK-SLC12A signal cascade is a new therapeutic target for hypertension].
abstract: WNK-oxidative stress-responsive 1 (OSR1) /STE20/SPS1-related proline-alanine-rich protein kinase(SPAK)-SLC12A transporters cascade regulates blood pressure through NaCl reabsorption in kidney and vasoconstriction. Furthermore, we recently reported that this cascade is positively regulated by insulin, which may contribute to hypertension in patients with hyperinsulinemia. Therefore, drugs that inhibit this signal cascade could become new antihypertensive drugs that have dual effects as a diuretic and vasodilator and be particularly beneficial for patients with hyperinsulinemia such as metabolic syndrome and obesity. In this review, we provide an overview about the current understanding about WNK-SPAK-SLC12A signal cascade and show some prospects for drug discovery that blocks this signal cascade.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D028021:Sodium-Potassium-Chloride Symporters; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases