BackgroundPuromycin aminonucleoside (PAN) nephropathy is a widely studied model of glomerular sclerosis (GS) in the rat, and cholesterol feeding exacerbates the injury induced by PAN. The importance of the interaction of angiotensin II (Ang II) with the AT2receptor is unclear. We investigated the role of the renin-angiotensin system, particularly with regard to AT1and AT2receptor dynamics, in PAN and cholesterol-mediated GS.MethodsSprague-Dawley rats were given a 4% cholesterol diet (group II), subcutaneous PAN (group III), or a 4% cholesterol diet and PAN (group IV) and compared with a control group given PAN vehicle (group I). After 16 weeks, kidneys were harvested and tissue Ang II concentration, angiotensin-converting enzyme (ACE) activity, and ACE, AT1, and AT2mRNA levels were determined.ResultsCompared with control rats, proteinuria was significantly higher in groups II to IV. Kidney ACE activity and ACE mRNA levels in groups III and IV were 2- and 3-fold higher than in groups I and II, respectively. Kidney Ang II concentration also was increased in the experimental groups. Whereas kidney AT1mRNA was significantly lower in groups III and IV, kidney AT2mRNA was significantly increased in groups II to IV.ConclusionIn these experimental models of GS, there is significant activation of the tissue-based renin-angiotensin system. Puromycin with and without cholesterol decreased the AT1receptor mRNA and increased the AT2receptor mRNA. Up-regulation of AT2receptors may be important in ameliorating the proliferative effects of Ang II, which presumably occur through the AT1receptor.