[WNK-SPAK-SLC12A signal cascade is a new therapeutic target for hypertension].

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.