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.
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.
Authors: Lucienne S Lara; Ryousuke Satou; Camille R T Bourgeois; Alexis A Gonzalez; Andrea Zsombok; Minolfa C Prieto; L Gabriel Navar Journal: Am J Physiol Renal Physiol Date: 2012-03-21
Authors: Matthew R Weir; Raymond R Townsend; Jeffrey C Fink; Valerie Teal; Stephen M Sozio; Cheryl A Anderson; Lawrence J Appel; Sharon Turban; Jing Chen; Jiang He; Natasha Litbarg; Akinlolu Ojo; Mahboob Rahman; Leigh Rosen; Susan Steigerwalt; Louise Strauss; Marshall M Joffe Journal: Am J Nephrol Date: 2012-10-12 Impact factor: 3.754