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Sex and age differences of renal function in rats with reduced ANG II activity during the nephrogenic period

Analia Loria1, Virginia Reverte, Francisco Salazar

  • 1Dept. of Physiology, School of Medicine, University of Murcia, 30100 Murcia, Spain.

American Journal of Physiology. Renal Physiology
|April 20, 2007
PubMed

Insights

Blocking angiotensin II during development accelerates kidney aging in male rats, impairing renal function and concentrating ability. These effects are more pronounced with age and differ between sexes.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Pharmacology

Background:

  • Angiotensin II plays a crucial role in renal development and function.
  • Understanding the long-term consequences of manipulating the renin-angiotensin system during development is essential for pediatric nephrology.
  • Sex and aging are known modulators of renal physiology and disease progression.

Purpose of the Study:

  • To investigate if blocking angiotensin II effects during early renal development accelerates aging-related changes in renal hemodynamics and proteinuria.
  • To determine if these accelerated changes are sex-dependent.
  • To examine if the deterioration of urinary concentrating ability due to angiotensin II blockade is sex and/or aging dependent.

Main Methods:

  • Newborn Sprague-Dawley rats were treated with an AT(1) angiotensin II receptor antagonist (ARA) or vehicle during the first 14 postnatal days.
  • Physiological parameters including blood pressure, glomerular filtration rate, proteinuria, and urinary concentrating ability were assessed at 3 and 11 months of age.
  • Urinary concentrating ability was evaluated in response to dehydration.

Main Results:

  • ARA treatment increased blood pressure similarly in both sexes, with a greater increase at 11 months than at 3 months.
  • Glomerular filtration rate decreased only in 11-month-old male ARA-treated rats.
  • Proteinuria increased in male rats at 3 months and in both sexes at 11 months, with a significantly greater increase in males.
  • Urinary concentrating ability was reduced only in ARA-treated males and worsened with age.

Conclusions:

  • Blockade of angiotensin II during renal development leads to significant deterioration of renal function.
  • These functional deficits, including impaired hemodynamics, increased proteinuria, and reduced concentrating ability, are dependent on sex and aging.
  • Early-life manipulation of the renin-angiotensin system has long-lasting, sex-specific consequences on kidney health.

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