Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology

Alex A. Gutsol, Taben M. Hale, Jean Francois Thibodeau, Chet E. Holterman, Rania Nasrallah, Jose W.N. Correa, Rhian M. Touyz, Chris R.J. Kennedy, Dylan Burger, Richard L. Hébert, Kevin D. Burns

Research output: Contribution to journalArticlepeer-review


Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis of hypertension were analyzed—chronic angiotensin (Ang) II–infused and renin-overexpressing (TTRhRen) mice, spontaneously hypertensive (SHR), and Goldblatt two-kidney one-clip (2K1C) rats. Mouse models, SHR, and the nonclipped kidney in 2K1C rats had no regular signs of hypertensive tubulopathy. Histopathology in animals was mild and limited to variations in the volume density of tubular lumen and epithelium, interstitial space, and interstitial collagen. Affected kidneys in animals demonstrated lesion values that are significantly different compared with healthy controls but correspond to mild damage if compared with hypertensive humans. The most substantial human-like hypertensive tubulopathy was detected in the clipped kidney of 2K1C rats. For the first time, our study demonstrated the regular presence of chronic progressive nephropathy (CPN) in relatively young mice and rats with induced hypertension. Because CPN may confound the assessment of rodent models of hypertension, proliferative markers should be used to verify nonhypertensive tubulopathy.

Original languageEnglish (US)
Pages (from-to)160-175
Number of pages16
JournalToxicologic pathology
Issue number4
StatePublished - Jun 2023


  • angiotensin II
  • chronic progressive nephropathy
  • hypertensive nephrosclerosis
  • renin
  • renovascular hypertension
  • spontaneously hypertensive rats

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology


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