Long-Term Betaine Supplementation Increases Creatinine Clearance and Upregulates MAS and AT2 Receptor Expression in

Mateusz Koper1, Kinga Jaworska2, Wojciech Kopacz2

  • 1Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland, mateuszkoper988@gmail.com.

Abstract

Insights

Chronic betaine supplementation improved kidney function in spontaneously hypertensive rats (SHRs). Betaine increased creatinine clearance and modulated the renin-angiotensin system (RAS), suggesting potential for preventing hypertensive kidney injury.

Area of Science:

  • Nephrology
  • Cardiovascular Research
  • Nutritional Science

Background:

  • Hypertension is a major cause of kidney dysfunction, often involving the renin-angiotensin system (RAS).
  • Betaine, an osmolyte, has shown renoprotective effects and increases diuresis in spontaneously hypertensive rats (SHRs).
  • Previous studies indicated acute betaine administration enhances diuresis in SHRs without altering blood pressure.

Purpose of the Study:

  • To investigate the long-term effects of betaine supplementation on renal function in SHRs.
  • To assess the impact of chronic betaine intake on the renal renin-angiotensin system (RAS) and betaine transporter expression in SHRs.

Main Methods:

  • Six-week-old male SHRs were administered 0.5% betaine in drinking water or tap water for 16 weeks.
  • Evaluated hemodynamics, serum and urine biochemistry, and renal mRNA expression of RAS components and betaine transporters (SLC6A12, SLC6A20).

Main Results:

  • Betaine-treated SHRs exhibited higher creatinine clearance with no significant change in arterial blood pressure.
  • Renal expression of angiotensinogen and AT1B receptor decreased, while MAS and AT2 receptor expression increased.
  • Region-specific regulation of betaine transporters was observed: reduced cortical SLC6A20 and medullary SLC6A12, but increased medullary SLC6A20.

Conclusions:

  • Chronic betaine supplementation enhances creatinine clearance and shifts renal RAS mRNA profile towards MAS and AT2 receptor predominance in SHRs.
  • These findings suggest betaine as a potential strategy for preventing hypertensive kidney injury.
  • Further research is needed to confirm improved glomerular filtration and functional activation of protective RAS pathways.

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