Postnatal renin-angiotensin system inhibition prevents renal damage from prenatal inflammation in rats

J Tradit Chin Med. 2020 Aug;40(4):646-653. doi: 10.19852/j.cnki.jtcm.2020.04.012.

Abstract

Objective: To assess the protective role of benazepril, an angiotensin-converting enzyme inhibitor, in renal damage caused by prenatal inflammation.

Methods: Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague- Dawley rats on gestation days 8, 10, and 12. After birth, offspring received either tap water or benazepril in water between 7 and 68 weeks. Blood pressure, blood urea nitrogen, creatinine, and 24-h urine volume were measured as indices of renal function. Hematoxylin, eosin, periodic acid-Schiff, and Sirius Red staining were used to evaluate renal damage.

Results: Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels. Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation.

Conclusion: Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation, our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.

Keywords: Benazepril; NF-kappa B; Prenatalinflammatoryexposure; Renin-angiotensin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Animals
  • Benzazepines / administration & dosage*
  • Blood Pressure / drug effects
  • Female
  • Humans
  • Kidney / drug effects*
  • Kidney / immunology
  • Kidney / injuries
  • Lipopolysaccharides / adverse effects
  • Male
  • Maternal Exposure / adverse effects*
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / drug therapy*
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / immunology
  • Rats
  • Renin-Angiotensin System / drug effects*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Lipopolysaccharides
  • NF-kappa B
  • benazepril