(724.5) Renal-Tubular SGK1 is Involved  in Blood Pressure Circadian Rhythm

Poster Board Number: E178

Lama Al-Qusairi (Johns Hopkins Medical School), Anne Debonneville (University of Lausanne), Matteo Stifanelli (University of Lausanne), Denis Basquin (University of Maryland), Olivier Staub (University of Lausanne)

As many physiological functions, blood pressure (BP) follows a circadian pattern that rises during the active and decreases during the inactive phase of the day. BP rise at the beginning of active phase (known in human as the “morning surge”) coincides with the increase in circulating glucocorticoids and aldosterone. Serum- and glucocorticoid-induced kinase (SGK1), a clock-controlled and aldosterone-induced gene, plays a role in BP regulation in human and animal models. However, a role of SGK1 in the BP circadian regulation has not been demonstrated. 

Using telemetry, we analyzed BP in the inducible renal-tubule specific Sgk1Pax8/LC1 model under basal and high-potassium diet (HKD; 5%K+). Our data show that, under basal conditions, renal SGK1 plays no role in BP regulation. After one week of HKD and despite largely unaffected mean arterial BP (MAP), Sgk1Pax8/LC1 mice exhibit altered day/night variations. More specifically, the increase in BP during the active phase (BP surge) was blunted in both systolic and diastolic BP. After 7 weeks of HKD, more profound defect in BP was observed in the mutants as they exhibit decreased MAP, together with a dysregulated circadian rhythmicity. The BP defect was associated with abnormal NCC and ENaC expression and processing. Altogether, our data suggest that i) The kidney plays a major role in setting the BP circadian rhythm. ii) BP surge requires the renal-tubule SGK1.