Abstract 264: Erythropoietin-induced Hypertension and Vascular Injury in Mice Overexpressing Human Endothelin-1 Was Attenuated by Exercise
Bibliographic record
Abstract
Background: Erythropoietin (EPO) is used to correct anemia in chronic kidney disease (CKD). EPO has been shown to increase blood pressure (BP) in patients and animals with CKD. This BP rise can be blunted by endothelin (ET) A receptor blockers. Chronic exercise prevents or reduces development of cardiovascular disease. However, it is unknown whether exercise prevents EPO-induced hypertension. We hypothesized that EPO treatment would exacerbate endothelin (ET)-1-induced vascular damage and increase BP, and that exercise training might prevent these effects. Methods: Eight to 10-week old male mice overexpressing human preproET-1 in the endothelium (eET-1) were treated with EPO (100 U/kg, s.c, 3 times/week) or not, and subjected to swimming exercise (1 h/d, 5 d/week) for 8 weeks or maintained in sedentary condition (n=7-8). Wild-type (WT) mice were also treated or not with EPO. Systolic BP (SBP) was measured by the tail-cuff method. Endothelial function was assessed in mesenteric arteries by pressurized myography. NADPH oxidase activity was assessed in aorta or renal cortex of by lucigenin chemiluminescence, reactive oxygen species (ROS) by dihydroethidium staining, and monocyte/macrophage and T regulatory cell (FoxP3) infiltration, and VCAM-1 by immunofluorescence staining. Results: EPO increased SBP by 24 mmHg ( P <0.05) and impaired vasodilatory responses to acetylcholine in eET-1 (68% vs. 91%, P <0.01). NADPH oxidase activity was 2-fold higher in eET-1 than in WT ( P <0.05), and further increased 1.5-fold by EPO ( P <0.01). ROS production in aorta of WT was enhanced 2-fold ( P <0.01) by EPO, which increased ROS in eET-1 a further 9-fold ( P <0.01). EPO increased monocyte/macrophage infiltration in aorta of WT 2.5-fold ( P <0.01), and in eET-1 a further 2.7-fold ( P <0.05). VCAM-1 expression in aorta was 2.7-fold higher in eET-1 than in WT ( P <0.05). All of the above was prevented by exercise ( P <0.05). Exercise with or without EPO increased T regulatory FoxP3 + lymphocytes in renal cortex 3-fold compared to eET-1 and WT ( P <0.01). Conclusions: Exercise prevents EPO-induced BP elevation and vascular damage through a mechanism involving decreased vascular oxidative stress and inflammation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".