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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/F317    most recent 90450.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakayama, T. Articles by Nakagawa, T. Search for Related Content PubMed PubMed Citation Articles by Nakayama, T. Articles by Nakagawa, T.

Endothelial injury due to eNOS deficiency accelerates the progression of chronic renal disease in the mouse

¹Division of Nephrology; ²Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida; ³Division of Nephrology, Showa University Fujigaoka Hospital, Kanagawa, Japan; and ⁴Division of Renal Disease and Hypertension, University of Colorado Denver, Aurora, Colorado

Submitted 3 August 2008 ; accepted in final form 21 November 2008

The vascular endothelium expresses endothelial nitric oxide synthase (eNOS) that generates nitric oxide (NO) to help maintain vascular integrity due to its anti-inflammatory, antiproliferative, and antithrombogenic effects. Pharmacological blockade of NO production has been shown to exacerbate renal injury in chronic renal disease and induces endothelial cell loss. However, pharmacological inhibition of NO nonspecifically blocks other types of NOS and therefore does not define the specific role of eNOS in kidney disease. We hypothesized that a lack of endothelial eNOS can induce a loss of glomerular and peritubular capillary endothelium and exacerbate renal injury in progressive renal disease. We tested out this hypothesis using remnant kidney (RK) in eNOS knockout (eNOS KO) mice. Systolic blood pressure was significantly higher, and renal function was worse in RK-eNOS KO mice compared with those in RK-C57BL6 mice. eNOS deficiency resulted in more severe glomerulosclerosis, mesangiolysis, and tubular damage. Glomerular and tubular macrophage infiltration and collagen deposition were also greater in RK-eNOS KO mice. Renal injuries in the RK-eNOS KO mice were accompanied by a greater loss of endothelial cells that was shown to be due to both a decrease in endothelial cell proliferation and an increase in apoptosis. A lack of eNOS accelerates both glomerular and tubulointerstitial injury with a loss of glomerular capillaries and peritubular capillaries. Impaired endothelial function is likely a direct risk factor for renal disease.

endothelial nitric oxide synthase; glomerular endothelial cell; mesangiolysis