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Updated: Jun 27, 2026

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
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.
Introduction:
Hypertension contributes to renal dysfunction, partly through dysregulation of the renin-angiotensin system (RAS). Betaine, an osmolyte that helps maintain medullary osmotic gradients, has demonstrated renoprotective effects in models of nephrotoxicity. Previously, we showed that acute betaine administration increases diuresis - more pronounced in spontaneously hypertensive rats (SHRs) than in normotensive Wistar-Kyoto rats - without affecting blood pressure. In this study, we investigated the effects of chronic betaine supplementation on SHR renal function.
Methods:
Six-week-old male SHRs received either 0.5% betaine in drinking water or tap water for 16 weeks. Hemodynamics, serum and urine biochemistry, and renal mRNA expression of RAS components and betaine transporters (SLC6A12, SLC6A20) were assessed.
Results:
Betaine-treated SHRs demonstrated higher creatinine clearance without significant changes in arterial blood pressure. Renal expression of angiotensinogen and AT1B receptor was reduced, while MAS and AT2 receptor expression increased. Transporter expression showed region-specific regulation: cortical SLC6A20 and medullary SLC6A12 were lower in betaine-treated rats, whereas medullary SLC6A20 was higher.
Conclusion:
Chronic betaine supplementation was associated with increased creatinine clearance and a renal RAS mRNA profile shifted toward MAS and AT2 receptor predominance. These findings support further investigation of betaine as a potential strategy for early prevention of hypertensive kidney injury. However, direct evidence of improved glomerular filtration and functional activation of protective RAS pathways is still needed.
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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