Novel mechanism of salt-induced glomerular injury: critical role of eNOS and angiotensin II

作者：Nakamura Taishi; Kataoka Keiichiro; Tokutomi Yoshiko; Nako Hisato; Toyama Kensuke; Dong Yi Fei; Koibuchi Nobutaka; Yamamoto Eiichiro; Yasuda Osamu; Ogawa Hisao; Kim Mitsuyama Shokei^*

来源：Journal of Hypertension, 2011, 29(8): 1528-1535.

DOI：10.1097/HJH.0b013e328348ca95

• angiotensin II
• eNOS
• glomerular angiotensinogen
• high salt
• oxidative stress

Objectives The present study was undertaken to examine the role of endothelial nitric oxide synthase (eNOS) in salt-sensitive renal injury.
Methods The effects of high-salt diet on renal injury were compared between wild-type and eNOS-/- mice. To examine the role of glomerular angiotensin II and oxidative stress, high-salt fed eNOS-/- mice were given irbesartan, an angiotensin receptor blocker, or tempol, an antioxidant.
Results Four weeks of high-salt diet in wild-type mice, which rapidly caused glomerular eNOS activation and subsequent increase in nitric oxide, did not at all induce renal injury, indicating that wild-type mice are salt-resistant. On the contrary, high-salt diet in eNOS-/- mice, which little increased nitric oxide, rapidly increased urinary albumin excretion, followed by glomerular macrophage infiltration and glomerular sclerosis. Thus, eNOS deficiency caused salt-sensitive glomerular injury. Salt-induced glomerular injury in eNOS-/- mice was preceded by rapid enhancement of glomerular superoxide followed by enhancement of glomerular endothelial angiotensinogen and angiotensin II. Irbesartan and tempol, independently of blood pressure, markedly prevented salt-induced glomerular injury in eNOS-/- mice, and these protective effects were attributed to the attenuation of glomerular oxidative stress and glomerular angiotensinogen-derived angiotensin II.
Conclusion We propose that eNOS dysfunction plays a causative role in salt-induced glomerular injury, through augmentation of glomerular oxidative stress-induced angiotensinogen.

• 出版日期2011-8