Tumor necrosis factor-α potentiates the effects of angiotensin II on subfornical organ neurons
Bibliographic record
Abstract
Inflammation is thought to play a fundamental role in the pathophysiology of hypertension and heart failure, although the mechanisms for this remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), influence the subfornical organ (SFO) to modulate sympathetic activity and blood pressure. The pressor effects of TNF-α in the SFO are partially mediated by angiotensin II (ANG II) receptor type 1 (AT 1 R), and TNF-α is known to potentiate ANG II-induced hypertension. However, the cellular mechanism of the interaction between TNF-α and ANG II/AT 1 R signaling remains unknown. In the present study, we performed Ca 2+ imaging on dissociated SFO neurons in vitro from male Sprague-Dawley rats to determine whether TNF-α modulates ANG II-induced increases in intracellular Ca 2+ in SFO neurons. We first established that a proportion of SFO neurons respond to ANG II, an effect that required AT 1 R signaling and extracellular Ca 2+ . We then tested the hypothesis that TNF-α may modulate the effects of ANG II on SFO neurons by examining the effects of TNF-α treatment on the ANG II-induced rise in intracellular Ca 2+ . We discovered that TNF-α potentiated the ANG II-induced rise in intracellular Ca 2+ , an effect that was dependent on the duration of TNF-α treatment. Finally, we determined that this potentiation of ANG II-induced Ca 2+ activity relied on tetrodotoxin-sensitive voltage-gated Na + (vgNa + ) channels. These data suggest that the potentiation of ANG II/AT 1 R activity by TNF-α in SFO neurons results from the previously demonstrated ability of this cytokine to modulate the activation threshold of vgNa + currents.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.007 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".