期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 146, 期 -, 页码 333-339出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2019.11.014
关键词
Hypertension; Reactive oxygen species; Immune cells; Renal damage; NADPH oxidase; p67phox
资金
- [HL116264]
- [HL137748]
- [DK62803]
- [AHA-15SFRN2391002]
- [19CDA34660184]
Previous studies utilizing the SSp67phox-/- rat have demonstrated the importance of systemic NADPH oxidase NOX2-derived reactive oxygen species (ROS) production in the pathogenesis of Dahl Salt-Sensitive (SS) hypertension and renal damage. It is established that the immune system contributes to the development of SS hypertension and our laboratory has observed an enrichment of NOX2 subunits in infiltrating T cells. However, the contribution of immune cell-derived ROS in SS hypertension remains unknown. To assess the role of ROS in immune cells, SSp67phox-/- rats underwent total body irradiation and received bone marrow transfer from either SS (+SS) or SSp67phox-/- (+SSp67phox-/-) donor rats. Demonstrated in a respiratory burst assay, response to phorbol 12-myristate 13-acetate stimulus (135 mu M) was 10.2-fold greater in peritoneal macrophages isolated from +SS rats compared to nonresponsive + SSp67phox-/- cells, validating that + SS rats were capable of producing NOX2-derived ROS in cells of hematopoietic origin. After 3 weeks of high salt challenge, there was an exacerbated increase in mean arterial pressure in +SS rats compared to + SSp67phox-/- control rats (176.1 +/- 4.7 vs 147.9 +/- 8.4 mmHg, respectively), which was accompanied by a significant increase in albuminuria (168.3 +/- 23.7 vs 107.0 +/- 20.4 mg/day) and renal medullary protein cast formation (33.2 +/- 4.7 vs 8.1 +/- 3.5%). Interestingly, upon analysis of renal immune cells, there was trending increase of CD11b/c + monocytes and macrophages in the kidney of +SS rats (4.7 +/- 0.4 vs 3.5 +/- 0.5 x 10(6) cells/kidney, +SS vs + SSp67phox-/-, p = 0.06). These data altogether demonstrate that immune cell production of NOX2-derived ROS is sufficient to exacerbate Dahl SS hypertension, renal damage, and renal inflammation.
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