Molecular dysregulation of the thiazide-sensitive sodium chloride cotransporter in the generation of primary hypertension

Hypertension, the leading global cause of premature death, is strongly influenced by renal ion transport mechanisms. This dissertation investigates the role of the thiazide-sensitive sodium chloride cotransporter (NCC) in two models of primary hypertension: adrenergic stimulation and low dietary potassium. Using animal models, we show that β-adrenergic receptors activate NCC via the OxSR1 kinase and that low potassium triggers NCC activation through intracellular chloride reduction and the WNK-SPAK/OxSR1 pathway. These findings provide mechanistic insight into NCC regulation and suggest novel therapeutic targets for more effective, personalized antihypertensive treatments.