Vimentin and heat shock protein expression are induced in the kidney by angiotensin and by nitric oxide inhibition

Background. Angiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with N^ω-nitro-L-arginine-methylester (L-NAME) are experimental models of hypertension associated with renal inflammation and oxidative stress. To gain insight into the nature of the tubulointerstitial injury induced in these models, we studied lectin-binding specificities, vimentin expression, and heat shock protein (HSP) 60 and 70 in these experimental models. Methods. Sprague-Dawley rats received Ang II infusion (435 ng/kg/min) for 2 weeks by subcutaneous minipumps (Ang II group, N = 5) or L-NAME in the drinking water (70 mg/100 mL) for 3 weeks (L-NAME group N = 7). The control group consisted of 10 rats. Systolic blood pressure (tail-cuff plethysmography), serum creatinine, and proteinuria were determined weekly. At the end of the treatment period, rats were sacrificed and kidneys studied. Binding specificities of fluorescein-labeled lectins were examined in frozen sections, and cellular infiltrates were identified by immunohistology and expression of vimentin and HSP 60 and 70 with immunohistochemistry and computer image analysis. Results. Tubulointerstitial accumulation of macrophages, lymphocytes, and Ang II-positive cells were present in the Ang II group and L-NAME group. Vimentin, HSP 60, and HSP 70 were increased 8 to 20 times in the cortex of the rats of the Ang II group and the L-NAME groups. Neoexpression of vimentin and HSPs was found primarily in proximal tubular cells. Conclusion. Ang II infusion and NOS inhibition induce tubular injury with epithelial cell transdifferentiation and expression of stress proteins. The role of these changes in the accumulation and activation of the interstitial inflammatory infiltrate merits further investigation.