Abstract P284: Increased Blood Pressure in Interleukin-6 Infused Mice is Secondary to Reduced Urinary Sodium Excretion and Not Vascular Dysfunction
Bibliographic record
Abstract
Hypertension (HTN) is associated with increased renal sodium (Na + ) reabsorption, vascular and endothelial dysfunction and an increase in cytokines, such as interleukin 6 (IL-6). We have previously shown that IL-6 increases blood pressure (BP), and increases the expression/activity of distal nephron Na + transport proteins via the mineralocorticoid receptor. We hypothesized that IL-6 increases Na + reabsorption, and induces endothelial dysfunction, leading to HTN. All mice were fed high salt food, and osmotic minipumps were implanted containing IL-6 (16 ng/hr, 0.01% BSA/saline), or vehicle/sham surgery (Ctl). To allow for early urine collection, IL-6 infusion was delayed by adding catheters to the minipumps during metabolic cage studies. Tail cuff plethysmography was used to measure systolic BP. Concentration response curves (CRC) to phenylephrine (Phe) and acetylcholine (ACh) were performed on aorta (Ao) and mesenteric arteries (Mes) from IL-6 or Ctl mice. IL-6 infused mice had increased BP by day 3 (D3), as compared to Ctl. Total urine volume (U Vol ) on D1 of infusion was reduced in IL-6 mice (U Vol 17.3±4 vs. 29.5±3 mL/day/per 100g body weight (BW); p<0.05), as compared to Ctl. This corresponded with a reduction in total urinary Na + excretion (U Na 81±19 IL-6 vs . 139±13 mg/day/BW Ctl; p<0.05). By D2, no differences in U Na were observed, and by D3 U Na levels were increasing in IL-6 infused mice. Similar trends for U Vol were observed. These results corresponded with our observed increases in BP. CRCs (D3) to Phe were not changed in Ao. However, Mes from IL-6 mice exhibited a surprising reduction in Phe-mediated contraction (136±7% vs. 155±5%; p<0.05), compared to Ctl. Similarly, Mes from IL-6 mice exhibited an increase in ACh-mediated relaxation responses (EC 50 -7.5±0.12 vs . -6.9±0.15; p<0.05). These data suggest that IL-6 increases BP via an early (D1) reduction in U Na /U Vol , followed by steady state recovery and pressure natriuresis (D3). Additionally, the increased relaxation and reduced contractility observed in the resistance arteries may suggest a compensatory response to the increased BP. Together, our studies suggest that in the early stages of HTN, cytokines may cause changes in renal Na + reabsorption via activation of distal Na + transporters.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.006 |
| Insufficient payload (model declined to judge) | 0.017 | 0.006 |
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".