Effect of angiotensin II on diabetic glomerular hyperpermeability: an in vivo permeability study in rats

Nima Nalin, Ali Al Dhanhani, Alia AlBawardi, Charu Sharma, Sanjana Chandran, Javed Yasin, Omran Bakoush

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2 Citations (Scopus)


Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg-1·min-1 for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ~20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (h) for inert polydisperse Ficoll molecules, which had a radius of 10–90 Å (Ficoll70–90 Å), were measured in vivo. The h for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (h for Ficoll70–90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (h for Ficoll70–90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.

Original languageEnglish
Pages (from-to)F833-F838
JournalAmerican Journal of Physiology - Renal Physiology
Issue number5
Publication statusPublished - Nov 3 2020


  • Angiotensin II
  • Diabetes mellitus
  • Diabetic nephropathy
  • Glomerular filtration barrier
  • Hypertension

ASJC Scopus subject areas

  • Physiology
  • Urology


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