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Expression of endothelial nitric oxide synthase is suppressed in the renal vasculature of angiotensinogen-gene knockout mice


We have attempted to elucidate the mechanism by which endothelial-type nitric oxide synthase (eNOS) is regulated in the kidney, with special reference to the role of renal hemodynamics and angiotensin II (Ang II). We compared angiotensinogen gene knockout (Atg−/−) mice, which lacked Ang II (resulting in sodium/water depletion and severe hypotension), with wild-type (Atg+/+) mice. Using Western blot analysis and the NADPH diaphorase histochemical reaction, we found that the expression and activity of eNOS were markedly lower in the renal vessels of Atg−/− mice compared with wild-type (Atg+/+) mice. Dietary salt loading significantly enhanced renal eNOS levels and increased blood pressure in Atg−/− mice, but severe hypotension almost abolished the effects of salt loading. In contrast, in Atg+/+ mice, altered salt intake or hydralazine had no effect on renal eNOS levels. These results suggest that perfusion pressure plays an essential role in maintaining renal vascular eNOS activity, whereas Ang II plays a supportive role, especially when renal circulation is impaired.

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Correspondence to Minoru Kihara.

Additional information

This study was supported by Grants-in-Aid for Scientific Resarch 2001–2003, Japan Society for Promotion of Science (grant no. 13670735).

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Kihara, M., Sato, K., Hashimoto, T. et al. Expression of endothelial nitric oxide synthase is suppressed in the renal vasculature of angiotensinogen-gene knockout mice. Cell Tissue Res 323, 313–320 (2006).

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  • Kidney
  • Nitric oxide synthase
  • Angiotensin II
  • Hypotension
  • Dietary salt loading
  • Perfusion pressure
  • Mouse (ICR, Atg+/+; Atg−/−)