Albuminuria indicates the pressure-associated injury of juxtamedullary nephrons and cerebral strain vessels in spontaneously hypertensive stroke-prone rats

Hypertens Res. 2012 Oct;35(10):1024-31. doi: 10.1038/hr.2012.112. Epub 2012 Aug 23.


Albuminuria is an indicator of renal injury and is closely linked with cardiovascular disease (CVD). However, the mechanism by which albumin is excreted in the urine remains unclear. As the juxtamedullary region of the kidney is highly susceptible to pressure increase, juxtamedullary injury is observed from an early phase in hypertensive rat models. Anatomical similarities are observed between the pre-glomerular vessels of the juxtamedullary nephron and the cerebral vasculature. We previously named these 'strain vessels' for their high vascular tone and exposure to higher pressures. The current studies were designed to determine whether albuminuria is the result of juxtamedullary nephron injury, indicating the presence of pressure injury to the strain vessels in spontaneously hypertensive stroke-prone rats (SHR-SP) fed a high-salt diet. Albuminuria was associated with juxtamedullary nephron injury, and the enhanced expression of monocyte chemotactic protein-1 (MCP-1) and tumor growth factor-beta (TGF-β) in 12-week-old SHR-SP rats fed a 4% high-salt diet from the age of 6 weeks. The wall thickness of the pre-glomerular vessels of the juxtamedullary nephron was also associated with that of the perforating artery of the middle cerebral artery. Reducing the blood pressure with nifedipine reduced the degree of albuminuria and juxtamedullary nephron injury as well as MCP-1 and TGF-β expression in the SHR-SP rats fed an 8% high-salt diet from the age of 9 weeks. Nifedipine inhibited stroke events in these animals until they were 14 weeks old. These results indicate that albuminuria is a result of juxtamedullary nephron injury and a marker of pressure-induced injury of the strain vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Albuminuria / etiology*
  • Animals
  • Arterioles / pathology
  • Blood Pressure
  • Brain / blood supply
  • Chemokine CCL2 / analysis
  • Juxtaglomerular Apparatus / pathology*
  • Male
  • Nephrons / pathology*
  • Rats
  • Rats, Inbred SHR
  • Stroke / etiology*
  • Transforming Growth Factor beta / analysis


  • Actins
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Transforming Growth Factor beta
  • smooth muscle actin, rat