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Angiotensin AT? receptor stimulation inhibits early renal inflammation in renovascular hypertension.


ABSTRACT: Angiotensin II type 2 receptor (AT?R) counteracts most effects of angiotensin II type 1 receptor (AT(1)R). We hypothesized that direct AT?R stimulation reduces renal production of the inflammatory cytokines tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), and transforming growth factor-?1 (TGF-?1) and enhances the production of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) in the clipped kidney of 2-kidney, 1-clip (2K1C) hypertension rat model. We used Sprague-Dawley rats to evaluate changes in renal interstitial fluid recovery levels of TNF-?, IL-6, NO, and cGMP; renal expression of AT?R, AT?R, TGF-?1, TNF-?, and IL-6 in sham and 2K1C rats treated for 4 days with vehicle, AT?R agonist compound 21 (C21), or AT?R antagonist PD123319 (PD), alone and combined (n=6, each group). Systolic blood pressure increased significantly in 2K1C and was not influenced by any treatment. Clipped kidneys showed significant increases in renal expression of AT?R, AT?R, TNF-?, IL-6, TGF-?1 and decreases in NO and cGMP levels. These factors were not influenced by PD treatment. In contrast, C21 caused significant decrease in renal TNF-?, IL-6, TGF-?1 and an increase in NO and cGMP levels. Combined C21 and PD treatment partially reversed the observed C21 effects. Compared to sham, there were no significant changes in TNF-?, IL-6, TGF-?1, NO, or cGMP in the nonclipped kidneys of 2K1C animals. We conclude that direct AT?R stimulation reduces early renal inflammatory responses and improves production of NO and cGMP in renovascular hypertension independent of blood pressure reduction.

SUBMITTER: Matavelli LC 

PROVIDER: S-EPMC3060557 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Angiotensin AT₂ receptor stimulation inhibits early renal inflammation in renovascular hypertension.

Matavelli Luis C LC   Huang Jiqian J   Siragy Helmy M HM  

Hypertension (Dallas, Tex. : 1979) 20101228 2


Angiotensin II type 2 receptor (AT₂R) counteracts most effects of angiotensin II type 1 receptor (AT(1)R). We hypothesized that direct AT₂R stimulation reduces renal production of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β1 (TGF-β1) and enhances the production of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) in the clipped kidney of 2-kidney, 1-clip (2K1C) hypertension rat model. We used Sprague-Dawley ra  ...[more]

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