Renal tubular SGK1 is required to achieve blood pressure surge and circadian rhythm.

Blood pressure (BP) follows a circadian pattern that rises during the active phase of the day (morning surge) and decreases during the inactive (night dipping) phase of the day. The morning surge coincides with increased circulating glucocorticoids and aldosterone, ligands for glucocorticoid receptors and mineralocorticoid receptors, respectively. Serum- and glucocorticoid-induced kinase 1 (), a clock-controlled and glucocorticoid receptor- and mineralocorticoid receptor-induced gene, plays a role in BP regulation in human and animal models. However, the role of in BP circadian regulation has not yet been demonstrated. Using telemetry, we analyzed BP in the inducible renal tubule-specific model under basal K diet (1% K) and high-K diet (HKD; 5% K). Our data revealed that, under basal conditions, renal plays a minor role in BP regulation; however, after 1 wk of HKD, mice exhibited significant defects in diastolic BP (DBP), including a blunted surge, a decreased amplitude, and reduced day/night differences. After prolonged HKD (7 wk), mice had lower BP than control mice and exhibited reduced DBP amplitude, together with decreased DBP day/night differences and midline estimating statistic of rhythm (MESOR). Interestingly, renal SGK1 deletion increased pulse pressure, likely secondary to an increase in circulating aldosterone. Taken together, our data suggest that ) the kidney plays a significant role in setting the BP circadian rhythm; ) renal tubule mediates the BP surge and, thus, the day/night BP difference; ) long-term renal deletion results in lower BP in mutant compared with control mice; and ) renal indirectly regulates pulse pressure due to compensatory alterations in aldosterone levels. Dysregulation of blood pressure (BP) circadian rhythm is associated with metabolic, cardiovascular, and kidney diseases. Our study provides experimental evidence demonstrating, for the first time, that renal tubule serum- and glucocorticoid-induced kinase 1 () plays an essential role in inducing the BP surge. Inhibitors and activators of SGK1 signaling are parts of several therapeutic strategies. Our findings highlight the importance of the drug intake timing to be in phase with function to avoid dysregulation of BP circadian rhythm.