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The renin-angiotensin system in kidney development
Y Chen1, D Lasaitiene, P Friberg
1Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
Acta Physiologica Scandinavica
|July 31, 2004
Summary
The renin-angiotensin system (RAS) is crucial for normal kidney development. Blocking angiotensin II type-1 (AT(1)) receptor signaling in developing kidneys causes significant renal abnormalities and impaired function.
Area of Science:
- Nephrology
- Developmental Biology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) plays a vital role in regulating blood pressure and fluid balance.
- Components of the RAS are highly expressed in the developing kidney, suggesting a role in renal morphogenesis.
Purpose of the Study:
- To review renal abnormalities induced by pharmacological blockade of the RAS in experimental animal models.
- To discuss the pathogenetic mechanisms underlying these abnormalities.
Main Methods:
- Pharmacological interruption of angiotensin II type-1 (AT(1)) receptor signaling in animals with ongoing nephrogenesis.
- Targeted gene inactivation in mice for key RAS components (renin, angiotensinogen, ACE, AT(1) receptor isoforms).
Main Results:
- Pharmacological blockade of AT(1) receptor signaling led to papillary atrophy, arteriolar wall thickening, tubular atrophy, interstitial expansion, and impaired urinary concentrating ability.
- Similar renal abnormalities were observed in gene-targeted mice lacking essential RAS components.
- These findings indicate that intact AT(1) receptor signaling is essential for normal renal development.
Conclusions:
- The renin-angiotensin system, particularly signaling through AT(1) receptors, is indispensable for normal kidney development.
- Disruption of RAS signaling during nephrogenesis results in specific, reproducible renal structural and functional defects.