期刊
HYPERTENSION
卷 79, 期 6, 页码 1180-1189出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.121.18643
关键词
kidney; macrophages; mechanistic target of rapamycin complex 1; perfusion; rats; Sprague Dawley
资金
- [P01 HL116264]
- [RO1 HL137748]
This study investigated the effects of a rapid rise in renal perfusion pressure on mTOR activation and immune cell infiltration in the kidneys. The results showed that the elevation of RPP resulted in activation of mTORC1 and infiltration of macrophages and T lymphocytes, leading to inflammatory response.
Background: The present study in Sprague-Dawley rats determined the effects of a rapid rise of renal perfusion pressure (RPP) upon the activation of mTOR (mechanistic target of rapamycin), and the effects upon the infiltration of CD68-positive macrophages/monocytes and CD3-positive T lymphocytes into the kidneys. Methods: RPP was elevated by 40 mm Hg for 30 minutes in male Sprague-Dawley rats while measuring renal blood flow and urine flow rate. Sham rats were studied in the same way, but RPP was not changed. Since initial studies found that the acute increase of RPP resulted in activation of mTORC1 (phosphorylation of S6(S235/236)), the effects of inhibition of mTORC1 with rapamycin pretreatment were then determined. Results: It was found that a 30-minute increase of RPP (approximate to 40 mm Hg) resulted in an 8-fold increase of renal sodium excretion which was blunted by rapamycin treatment. Renal blood flow was not affected by the elevation of RPP. Activation of mTORC1 was observed. Significant increases in CD68-positive macrophages were found in both the cortex (intraglomerular and periglomerular regions) and in the outer medullary interstitial regions of the kidney and prevented by rapamycin treatment. Increases in CD3-positive T lymphocytes were observed exclusively in the periglomerular regions and prevented by rapamycin treatment. Upregulation of several proinflammatory markers was observed. Conclusions: We conclude that elevation of RPP rapidly activates mTORC1 resulting in infiltration of immune cells into the kidney.
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