Brain‐derived neurotrophic factor causes chloride gradient collapse in supraoptic neurons inducing vasopressin‐mediated blood pressure increase (LB847)
Bibliographic record
Abstract
Vasopressin (VP), an antidiuretic hormone, is also a potent vasoconstrictor and has been found at high levels in salt‐sensitive hypertensives. Hypertension normally reduces VP secretion by MNCs in the SON, by GABA‐dependent synaptic inhibition of their firing activities. However, in rats under chronic hypernatremia, GABAA receptor‐mediated synaptic inhibition is abolished in SON neurons due to a depolarization in chloride reversal potential (ECl), suggesting that continued VP secretion despite BP elevations may underlie the development of salt‐dependent hypertension. In order to test this hypothesis, we measured the mean arterial pressure (MAP) by radio telemetry in freely moving rats made chronically hypernatremic by 2% saline drinking. MAP of these rats rose steadily rise during the course of the 7‐day SL treatment (basal BP: 97.7±1.9 mmHg; day 7: 113.5±2.1 mmHg; n=10; P<0.05), however remained stable in euhydrated rats over the same time period (basal BP: 98.3±2.5 mmHg; day 7: 100.6±2.2 mmHg; n=6; P=0.50). Furthermore, the SL‐mediated increase in MAP was significantly reduced by continuous systemic infusion of a VP receptor type 1 (V1R) antagonist (αday 7; +8.8±2.5 mmHg; n=6) when compared to SL controls (α15.1±1.0 mmHg; n=10; P<0.05). These findings confirm our hypothesis that circulating VP contributes to increases in BP during chronic hypernatremia. Brain‐derived neurotrophic factor (BDNF) is a high‐affinity TrkB agonist previously shown to be responsible for chloride gradient collapse. In order to investigate this possibility in the SON, we induced a specific knockdown of this protein in SL rats in vivo by stereotaxic injections of adeno‐associated virus (AAV) containing BDNF‐shRNA into the SON. ECl measurements via Gramicidin perforated patch‐clamp revealed that this treatment significantly hyperpolarized the ECl of SON neurons (‐56.2±5.4 mV; n=10) when compared to values measured in SL rats injected with control AAV containing a scrambled sequence of shRNA (‐40.1±2.4 mV; n=7; p<0.05). These results strongly suggest that BDNF is the TrkB agonist responsible for producing the chloride gradient collapse in SON neurons under chronic hypernatremia, a phenomenon which potentially underlie the development of salt‐sensitive hypertension. Funding source: Canadian Institutes of Health Research. Grant Funding Source : CIHR
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".