Abstract Body: BACKGROUND: Blood pressure (BP) typically decreases during sleep, known as the “dipping” pattern. A “non-dipper”, characterized by <10% BP reduction during sleep, has an elevated cardiovascular risk. Intermittent hypoxia (IH) is used to model hypertension with sleep apnea, but its relation with BP dipping and its effect on the kidney remains unclear.
METHODS: Male C57BL/6J mice were kept under 12-hours light/dark cycles exposed to either normoxia (NX) or IH (O₂ concentration reduced to 5% in 90 seconds every 3 minutes during 8 hours within the light period, for >1 week). BP was measured by radiotelemetry, and the dipping state was assessed by comparing mean BP (MBP) between light and dark periods. Low-salt diet (0.05% NaCl) and Slc12a3^-/- mice (NCC-KO) were used to study the role of renal sodium transporters.
RESULTS: Mice kept under NX showed a dipping BP pattern, while those under chronic IH exhibited a non-dipping pattern. Low-salt diet restored the dipping pattern in the mice exposed to chronic IH. Under chronic IH, phosphorylation of NCC and NKCC2 in the kidney was increased, without changes in ENaCα cleaving. NCC-KO mice under NX displayed a dipping pattern of BP but, under chronic IH, shifted to the non-dipping. Furosemide administration restored the dipping pattern in NCC-KO mice exposed to chronic IH.
CONCLUSIONS: Chronic IH disrupts the physiological dipping pattern of BP through NCC and NKCC2 activation. This study underscores the kidney’s role in the non-dipping BP pattern caused by chronic IH, providing insights into the pathophysiology of non-dippers with sleep apnea.