ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO517

Circadian Rhythm Misalignment Induced Differential Expression of Mineralocorticoid Receptor Type I and Aldosterone in Kidneys and Urine of Male Rats

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Cholankeril, Tyler, Rowan University Cooper Medical School, Camden, New Jersey, United States
  • Roccato, Margaret, Rowan University Cooper Medical School, Camden, New Jersey, United States
  • Martinez, Diana, Rowan University Cooper Medical School, Camden, New Jersey, United States
  • Disanto, Michael E., Rowan University Cooper Medical School, Camden, New Jersey, United States
Background

Circadian rhythm misalignment (CRM) adversely impacts health and increases blood pressure (BP), especially in shift workers. Aldosterone (ALD) acting through mineralocorticoid receptor-1 (MCR1) causes sodium retention and water reabsorption to increase BP. The aim of this study was to determine if CRM alters the expression of MCR1 in the kidneys and aldosterone levels in the urine of rats.

Methods

32 young male rats were divided into control (CTL) and CRM groups. CTLs experienced normal light/dark cycles but CRMs were phase-advanced every 2 days for 22 days after which BPs were measured at 6-hour intervals. Rats were sacrificed and kidney tissue and urine stored at 80°C. RNA was extracted and Real-Time PCR conducted. ELISA was utilized to quantitate urine ALD. The MCR1 expression was normalized to 18s ribosomal RNA. An independent sample two-tailed t-test was used to determine effects of variance in both directions for both ELISA and RT-PCR data.

Results

Overall MCR1 expression was ~7.5-fold higher in combined CRM groups compared to CTL (p = 0.00019). Subgroup analyses revealed significance in the 9AM CRM group with an ~18-fold higher MCR1 expression (p = 0.20). The 3PM, 9PM and 3AM CRM groups also exhibited higher expression but did not reach statistical significance (Fig. 1). ALD was ~1.8-fold higher in combined CRM compared to CTL groups (p <0.0035). Subgroup analyses revealed the 9AM, & 3PM CRM groups with significantly higher ALD expression (~2.96-fold (p = 0.005) and ~ 2.87-fold (p = 0.011), respectively). 3AM also showed higher expression but the 9PM CRM subgroup did not differ from CTL.

Conclusion

MCR1 expression and ALD are upregulated in kidneys and urine of rats after CRM and may be a potential mechanism for CRM-induced renal and cardiovascular dysfunction (CVD). Additionally, MCR1 expression and ALD levels appear to vary over a daily 24-hour cycle. Shift workers, have an increased risk of impaired sodium excretion and water retention. We hypothesized that this impaired cycle is due to the improper activation of the renin-aldosterone-angiotensin system thus resulting in hypertension, renal dysfunction, and CVD.