Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function
Autor: | Deborah L. Donohoe, Kelly Roethe, Jeffrey L. Osborn, David P. Basile |
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Rok vydání: | 2001 |
Předmět: |
Male
medicine.medical_specialty Physiology Urinary system Ischemia Natriuresis Diuresis Renal function Blood Pressure Urine Kidney urologic and male genital diseases Peritubular capillaries Kidney Concentrating Ability Rats Sprague-Dawley Transforming Growth Factor beta1 Transforming Growth Factor beta Internal medicine medicine Animals RNA Messenger Dehydration Renal ischemia business.industry Osmolar Concentration Acute Kidney Injury medicine.disease Fibrosis Capillaries Rats Surgery Proteinuria Kidney Tubules medicine.anatomical_structure Reperfusion Injury Cardiology business Kidney disease |
Zdroj: | American Journal of Physiology-Renal Physiology. 281:F887-F899 |
ISSN: | 1522-1466 1931-857X |
DOI: | 10.1152/ajprenal.00050.2001 |
Popis: | First published August 9, 2001; 10.1152/ajprenal.00050.2001.—Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within ∼1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-β1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an ∼30–50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng · kg−1· min−1). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis. |
Databáze: | OpenAIRE |
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