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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
PubMed

Insights

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.

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