{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:27:28Z","timestamp":1774902448596,"version":"3.50.1"},"reference-count":25,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1152\/ajprenal.90450.2008","type":"journal-article","created":{"date-parts":[[2008,11,27]],"date-time":"2008-11-27T01:54:40Z","timestamp":1227750880000},"page":"F317-F327","source":"Crossref","is-referenced-by-count":80,"title":["Endothelial injury due to eNOS deficiency accelerates the progression of chronic renal disease in the mouse"],"prefix":"10.1152","volume":"296","author":[{"given":"Takahiro","family":"Nakayama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waichi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Campbell-Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashio","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byron P.","family":"Croker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiko","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.268.5.F885"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(12)80170-3"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2003.10.024"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.4.601"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.3.656"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1081\/IMM-55807"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060610"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Fujihara CK, De Nucci G, Zatz R.Chronic nitric oxide synthase inhibition aggravates glomerular injury in rats with subtotal nephrectomy.J Am Soc Nephrol5: 1498\u20131507, 1995.","DOI":"10.1681\/ASN.V571498"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199706)171:3<252::AID-JCP3>3.0.CO;2-N"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00085.2004"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64957-7"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03361"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64175-2"},{"key":"R14","unstructured":"Kang DH, Hughes J, Mazzali M, Schreiner GF, Johnson RJ.Impaired angiogenesis in the remnant kidney model: II. 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