Treatment with valsartan stimulates endothelial progenitor cells and renal label-retaining cells in hypertensive rats.

Abstract

OBJECTIVE:

The pathogenesis of hypertension is dependent on tissue angiotensin (Ang) II, which induces cardiovascular and renal remodeling. The presence of label-retaining cells (LRCs) as renal stem cells has been reported in nephrotubulus. We examined effects of treatment with valsartan on endothelial progenitor cells (EPCs) and renal LRCs in stroke-prone spontaneously hypertensive rats (SHR-SP).

METHODS:

SHR-SP were salt-loaded and treated with hydralazine or valsartan. Peripheral blood mononuclear cells (MNCs) were cultured to assess EPC colony formation and migration. LRCs were labeled for 1 week with bromodeoxyuridine (BrdU) and were detected after a 2-week chase period. We measured expression of c-kit and Pax-2 mRNAs in renal medulla.

RESULTS:

Colony formation and migration of EPCs were suppressed in salt-loaded SHR-SP. Treatment with valsartan markedly stimulated these EPC functions. There was no difference in the number of renal LRCs in normotensive Wistar-Kyoto rats and SHR-SP. Treatment with valsartan significantly improved renal tubular degeneration and increased the number of LRCs in renal medulla from salt-loaded SHR-SP. Treatment with valsartan significantly increased expression of c-kit and Pax-2 mRNAs in renal medulla from salt-loaded SHR-SP.

CONCLUSION:

These findings suggest that ARBs have cardiovascular and renal protective effects through an antioxidative action that stimulates ECP function and increases the number of the self-repairing renal LRCs.

• Authors: Yoshinori Yoshida, Noboru Fukuda, Akito Maeshima, Chii Yamamoto, Taro Matsumoto, Takahiro Ueno, Yoshihisa Nojima, Koichi Matsumoto, Masayoshi Soma
• Journal: Journal of hypertension (J Hypertens) Vol. 29 Issue 1 Pg. 91-101 (Jan 2011) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 20935578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• DNA Primers
• PAX2 Transcription Factor
• Pax2 protein, mouse
• Tetrazoles
• Thiobarbituric Acid Reactive Substances
• Valsartan
• Proto-Oncogene Proteins c-kit
• Valine

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Base Sequence
• Cell Movement
• DNA Primers
• Endothelium, Vascular (cytology, drug effects)
• Kidney Medulla (cytology, drug effects, metabolism)
• Male
• Oxidative Stress
• PAX2 Transcription Factor (metabolism)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-kit (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Stem Cells (cytology, drug effects)
• Tetrazoles (pharmacology)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Valine (analogs & derivatives, pharmacology)
• Valsartan