Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Molecular Biology

Background:

• Potassium-deficient diets are linked to increased blood pressure and salt sensitivity.
• A kidney pathway, the K+ switch, couples potassium sensing to NaCl retention via the NCC transporter, but its causal role is unproven.

Purpose of the Study:

• To investigate the causal role of the K+ switch pathway in translating plasma potassium levels to blood pressure regulation.
• To determine if activating the downstream kinase SPAK in the distal tubule affects blood pressure and NaCl handling.

Main Methods:

• Generated constitutively active SPAK (CA-SPAK) mice to genetically activate the K+ switch pathway in the kidney distal convoluted tubule.
• Monitored arterial blood pressure via radiotelemetry during a 4-day potassium titration in CA-SPAK and control mice.
• Assessed renal function, NCC abundance, phosphorylation, and activity in response to varying dietary potassium and NaCl.

Main Results:

• In control mice, decreasing plasma potassium increased blood pressure and NaCl sensitivity, with elevated NCC phosphorylation and sodium retention.
• CA-SPAK mice exhibited elevated blood pressure resistant to potassium changes, alongside sustained NCC activation and urinary sodium retention.
• Genetically activating the K+ switch pathway mimicked the effects of low potassium, increasing salt sensitivity and preventing blood pressure normalization.

Conclusions:

• The K+ switch pathway is causally involved in regulating blood pressure and NaCl sensitivity.
• Low potassium intake, prevalent in processed foods, activates this pathway, leading to increased sodium retention, higher blood pressure, and salt sensitivity.