Abstract 060: POLDIP-2/NOX-4 Generates Hydrogen Peroxide that Impairs Myogenic Response of Afferent Arterioles from Mice with the Reduced Renal Mass Model of Chronic Kidney Disease
| Autor: | Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K Griendling, W.Robert Taylor, William J Welch, Wilcox S Christopher |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Hypertension. 66 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Background: Because we have found that myogenic contractions are stimulated by superoxide (O 2 .- ) but inhibited by hydrogen peroxide (H 2 O 2 ), we tested the hypothesis that H 2 O 2 is the cause of the impaired myogenic responses of afferent arterioles from mice with the reduced renal mass (RRM) model of chronic kidney disease (CKD). Methods: Mice were subjected to 5/6 surgical nephrectomy or sham operations and fed 6% salt for 3 months. Single afferent arterioles were perfused, their diameter measured directly and O 2 .- and H 2 O 2 measured by fluorescence microscopy. Results: The perfusion pressure of isolated afferent arterioles was increased from 40 to 80 mmHg to study myogenic responses. Arterioles from mice with RRM (vs sham) had a greater increase in O 2 .- (21.2 ± 1.9 versus 11.3 ± 2.5%; p < 0.01) and especially H 2 O 2 (28.7 ± 3.7 versus 4.2 ± 0.4%, P2 .- by PEG-SOD (+3.3 ± 1.5 versus -1.7 ± 4.3%, Pphox (+2.5 ± 1.4 versus -1.7 ± 4.3%, P2 O 2 by PEG-catalase (-19.1 ± 1.6 versus -1.7 ± 4.3%, P2 O 2 ) was increased 40-50% (P Conclusions: Afferent arterioles from mice with RRM had severely impaired myogenic responses that were attributed to increased H 2 O 2 generation from POLDIP-2/NOX-4 that may therefore be novel targets to maintain autoregulation and protect kidneys from barotrauma in CKD. |
| Databáze: | OpenAIRE |
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