Estrogen in the Paraventricular Nucleus Attenuates <scp>l</scp> -Glutamate–Induced Increases in Mean Arterial Pressure Through Estrogen Receptor β and NO
Bibliographic record
Abstract
Estrogen (E2) acts in the brain to decrease blood pressure (BP) responses to psychological stress. A likely site for the effects of E2 is the hypothalamic paraventricular nucleus (PVN), an important regulator of autonomic functions. We studied the effects of E2 in the PVN on BP and heart rate (HR) responses to l-glutamate injections into the PVN of male urethane-anesthetized rats. Microinjections of l-glutamate (50 nmol) into the PVN increased BP by 14+/-2.5 mm Hg and HR by 30+/-5.6 bpm. Microinjections of E2 (0.1, 1, and 10 pmol) into the PVN 30 minutes before l-glutamate dose-dependently attenuated the pressor response by 25%, 34%, and 59%, respectively, but did not affect HR. We determined that E2 receptor (ER) beta mediates the effect of E2, because activation of ERbeta with diarylpropionitrile (50 pmol) attenuated the response by 57%, whereas activation of ERalpha with propyl-pyrazole-triol (20 pmol) had no effect. Furthermore, inhibition of ERbeta with R,R-tetrahydrochrysene (50 pmol) blocked the effect of E2, but inhibition of ERalpha with methyl-piperidino-pyrazole (1 nmol) did not. Finally, we found that the effect of E2 is mediated by NO, because the NO synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (2 nmol), the neuronal NOS inhibitor, 7-nitroindazole sodium salt (0.1 pmol), and the endothelial NOS inhibitor, N5-(1-iminoethyl)-l-ornithine (200 pmol) blocked the effect of E2. The effect was partially blocked with the gamma-aminobutyric acid(A) receptor inhibitor bicuculline. Our results demonstrate that E2 in the PVN attenuates the l-glutamate-induced pressor response and that this effect is mediated by ERbeta, NO produced by neuronal NO synthase and eNOS, and partly by gamma-aminobutyric acid.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| 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".