Published online before print May 27, 2003, doi: 10.1161/01.HYP.0000075082.06183.4E
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(Hypertension. 2003;42:31.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury
From the Division of Nephrology and Endocrinology, University of Tokyo School of Medicine (J.S., M.N., K.Y., T.F.), Tokyo, and the Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine (T.M., R.I., K.K.), Isehara, Kanagawa, Japan.
Correspondence to Dr Masaomi Nangaku, Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail mnangaku-tky{at}umin.ac.jp
Blockade of angiotensin (Ang) II is efficient in various renal diseases. Although interest has focused on the hemodynamic changes and reduction of proteinuria, recent studies emphasize the nonhemodynamic effects of Ang II on kidney injury. The aim of this study was to clarify the mechanisms of Ang II on the immune system that alter the balance of helper T-cell (Th) subsets. We used a continuous, Ang II infusion model of rats that develop hypertension, proteinuria, and tubulointerstitial damage, including de novo expression of 
-smooth muscle actin and loss of endothelial cells. We isolated T cells from the spleen and measured cytokine levels by ELISA systems. Ang II–infused rats showed an increase in the Th1 cytokine 
-interferon and a decrease in the Th2 cytokine interleukin-4. The same change in cytokine mRNA expression in the spleen and kidney was confirmed by quantitative polymerase chain reaction analysis. Our ELISPOT assay showed an increase in the number of -interferon–secreting T cells by Ang II. To investigate whether these changes were specific effects of Ang II, we treated the model rats with the Ang II receptor blocker (ARB) olmesartan or the nonspecific vessel dilator hydralazine. Administration of the ARB ameliorated disease manifestations and the imbalance in Th subsets, whereas hydralazine did not, despite comparable effects on blood pressure. These results demonstrate a direct role of Ang II in the modification of Th balance. The imbalance of Th subsets was associated with hypertensive kidney injury induced by Ang II. Some of the beneficial effects of ARBs might be explained by their immunomodulatory reactions.
Key Words: angiotensin • angiotensin II type 1 receptor blocker • helper T cell • tubulointerstitial damage • cytokines
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