Role of the H,K‐ATPase type 2 in the regulation of blood pressure during K + depletion (860.8)

Alteration of blood pressure (BP) level is one of the side effects associated to K+‐depletion. However, the mechanisms linking K+ balance to BP remain unsettled and debated. Adaptation to K+‐depletion requires ability to retain K+. In kidney and colon, this is handled by the stimulation of H,K‐ATPase type 2 (HKA2) and its absence leads to severe K+‐depletion under low‐K+ diet condition. Our aim is to investigate whether HKA2 may contribute to determination of BP level under low‐K+ diet. Wild‐type mice (WT) displayed a decrease of BP after 10 days of low‐K+ diet (from 113 to 103 mm Hg). In HKA2‐null mice, the decrease of BP (109 to 100 mm Hg) occurred much earlier (day 2‐3). At early stage of K+‐depletion, plasma volume remained constant in WT but decreased by 20% in HKA2‐null mice, indicating that decrease of BP is linked to a problem of volemia. However, this decrease of BP and volemia are not related to a leak of Na+ and fluid by the kidney. On the contrary, this hypovolemic state stimulates urinary Na+ retention through thiazide‐ and amiloride‐sensitive Na+ transport. Measurements of tissue Na+ contents suggest that the origin of the hypovolemia could be a transfer of fluid from the extracellular space toward the intracellular compartment. Presence of HKA2 is therefore required to limit the decrease of plasma K+ value and to protect against development of hypotension. Grant Funding Source : Supported by the Fondation du Rein