Null mutation of the p67phox subunit of NOX2 permits compensatory changes in renal blood flow during the development of salt-sensitive hypertension in SS rats

NOX2 的 p67phox 亚基的无效突变允许 SS 大鼠在盐敏感性高血压发展过程中肾血流量发生代偿性变化。

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Abstract

In the current study, we used SS(p67phox-/-) to assess the involvement of oxidative stress in the regulation of renal blood flow during the development of salt-sensitive hypertension in Dahl salt-sensitive (SS) rats. We performed continuous assessment of mean arterial blood pressure (MAP) and renal blood flow (RBF) over a 2-wk period using radiotelemetry and ultrasound flow probes, respectively. In initial time control studies, we confirmed the stability of the surgical preparation in Sprague-Dawley rats. We next assessed MAP and RBF in male SS and SS(p67phox-/-) during 2 wk of a high-salt (4.0% NaCl) diet. As we have previously shown, the hypertensive response to a high-salt diet was blunted in SS(p67phox-/-) rats compared with SS rats. RBF increased significantly with a high salt in the SS(p67phox-/-) rats. In contrast, although RBF was higher at baseline in SS rats than SS(p67phox-/-) rats, there was no significant increase with high salt in the SS rats. Consequently, by the end of the 2-wk study, renal blood was equivalent in both groups. Using circadian analysis, we found that both MAP and RBF have circadian rhythms. These rhythms were not synchronous at baseline, with the nadir of RBF preceding that of MAP. This separation between rhythms was exacerbated by high salt. In conclusion, using chronic assessment of MAP and RBF, we have shown that when p67(phox) is not functional in SS rats, high-salt causes a significant increase in RBF, and this is associated with a blunted hypertensive response. NEW & NOTEWORTHY Continuous measurements of MAP and RBF were made in conscious SS(p67phox)(-/-) rats to determine the role of oxidative stress in their regulation. Deletion of p67(phox) restored the vasodilatory response to a high-salt diet in SS rats. RBF increased in response to a salt load in SS(p67phox)(-/-) but not SS rats. Circadian analysis demonstrated that MAP and RBF became asynchronous as the rats progressed through the high-salt challenge: RBF peaked over 4 h before MAP.

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