Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide
Bibliographic record
Abstract
Adrenomedullin (ADM) acts in a site-specific manner within autonomic centers of the brain to modulate mean arterial pressure (MAP). To determine the role of ADM in the pontine autonomic center, the lateral parabrachial nucleus (LPBN), we used urethane-anesthetized adult Sprague-Dawley male rats to test the hypothesis that ADM increases MAP at this site through glutamate- and nitric oxide (NO)-dependent mechanisms. ADM microinjected into the LPBN increased MAP in a dose-dependent manner. The pressor effect of ADM (0.01 pmol) had a peak value of 11.9 +/- 1.9 mmHg at 2 min and lasted for 7 min. We demonstrated that ADM's effect is receptor mediated by blocking the effect with the ADM receptor antagonist, ADM22-52. We showed that glutamate mediates ADM's pressor response, as this response was blocked using coinjections of ADM with dizolcipine hydrogen maleate or 6-cyano-7-nitroquinoxaline-2,3-dione, N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists, respectively. We tested the roles of NO with coinjections of ADM with either N5-(1-iminoethyl)-L-ornithine or 7-nitroindazole monosodium salt, nonspecific and neuronal NO synthase (NOS) inhibitors, respectively; both inhibitors blocked ADM's pressor effect. Finally, we studied the role of calcium influx in ADM's pressor effect, as intracellular calcium is important in both glutamate and NO neurotransmission. ADM's effect was blocked when nifedipine, an L-type calcium channel blocker, was coinjected with ADM into the LPBN. This study is the first to show that ADM acts in the LPBN to increase MAP through mechanisms dependent on activation of ionotropic glutamate receptors, neuronal and endothelial NOS-mediated NO synthesis, and L-type calcium channel activation.
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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 | 0.000 |
| 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 | 0.001 |
| 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".