Salt-Sensitive Hypertension Begins With Intracellular K + and Water Loss
Shintaro Minegishi, Norihiko Morisawa, Johannes Wild, Yam Wan Keat, Kaoru Takase-Minegishi, Adriana Marton, Tzy Tiing Lim, Manuela Peukert, Regina Lohmayer, Stephen Walsh, Keith Siew, Manfred Rauh, Friedrich C. Luft, Jean-Paul Kovalik, Melanie Hoenig, Troy H. Puar, Kento Kitada, Jens TitzeBACKGROUND:
Na + and water overload due to inappropriately low renal salt and water excretion is considered the root cause of salt-sensitive hypertension. However, experimental renal and psoriasis hypertension are characterized by chronic predisposition to dehydration. We tested the validity of this alternative hypertension due to loss of water theory in deoxycorticosterone acetate (DOCA) salt-sensitive hypertension.
METHODS:
We tested the effect of DOCA (25 mg pellet) in mice on a low Na + diet (0.02%–0.03%) with tap water, or with Na + in their drinking water (1% NaCl or 1.44% NaHCO 3 ), on body Na + , K + , and water content 2, 6, and 12 days after treatment initiation. We monitored blood pressure with radio-telemetry, food and water intake, and renal electrolyte and water excretion.
RESULTS:
At day 2, DOCA NaCl-treated mice elevated blood pressure during a state of isolated body K + and water loss, indicating substantial intracellular dehydration. Although increasing their fluid intake and urine output, the mice reduced the excretion of free water, indicating renal water conservation. At days 6 and 12, secondary Na + retention occurred, which replaced the amount of K + lost and corrected the dehydration, albeit at the expense of an intracellular Na + /K + redistribution disorder. DOCA NaHCO 3 -treated mice with Na + -resistant blood pressure showed a comparable Na + /K + redistribution disorder, but without accompanying early dehydration due to earlier replacement of lost K + by Na + .
CONCLUSIONS:
Experimental DOCA salt-sensitive hypertension initiates with a systemic water conservation response in the face of K + -driven intracellular water loss. Both dehydration and blood pressure increase could be causally treated by oral K + supplementation.