Renal-Tubular SGK1 is Required to Achieve Blood Pressure Surge and Circadian Rhythm

Am J Physiol Renal Physiol. 2023 Sep 7. doi: 10.1152/ajprenal.00211.2023. Online ahead of print.ABSTRACTBlood pressure (BP) follows a circadian pattern that rises during the active (morning surge) and decreases during the inactive (night dipping) phase of the day. Morning surge coincides with increased circulating Glucocorticoids and Aldosterone, ligands for GR and MR nuclear receptors respectively. Serum- and glucocorticoid-induced kinase (SGK1), a clock-controlled and GR- and MR-induced gene, plays a role in BP regulation in human and animal models. However, the role of SGK1 in BP circadian regulation has not yet been demonstrated. Using telemetry, we analyzed BP in the inducible renal-tubule specific Sgk1Pax8/LC1 model under basal (1%K+) and high-potassium diet (HKD:5%K+). Our data revealed that, under basal conditions, renal SGK1 plays a minor role in BP regulation; however, after one week of HKD, Sgk1Pax8/LC1 mice exhibit significant defects in the diastolic BP (DBP), including a blunted surge, a decreased amplitude, and reduced day/night differences. After prolonged HKD (7 weeks), Sgk1Pax8/LC1 mice had lower BP than control mice, and exhibited reduced DBP amplitude, together with decreased DBP day/night differences and MESOR. Interestingly, renal SGK1 deletion increased pulse pressure, likely secondary to an increase in circulating Aldosterone. Altogether, our data suggest that i) The kidney plays a significant role in setting the BP circadian rhythm. ii) The renal-tubu...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Source Type: research