Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex control of heart rate: a role for protein kinase A
Bibliographic record
Abstract
1 The rostral ventrolateral medulla (RVLM) is an essential vasomotor center in the brainstem which participates in maintaining resting levels of arterial pressure and for regulating baroreflex activity. We have demonstrated that microinjections of adrenomedullin (ADM), a vasoactive neuropeptide, into the RVLM cause increased resting mean arterial pressure (MAP) and heart rate (HR). However, the effect of ADM on baroreflex function remains unclear. 2 The purposes of the present study were to investigate the effect of ADM in the RVLM on the regulation of baroreflex activity and to identify the underlying mechanisms. Baroreflex curves were generated with intravenous injections of multiple doses of phenylephrine and nitroprusside. The upper and lower plateaus, reflex range, MAP at the midpoint of HR range (MAP(50)), and gain were evaluated before and after various microinjections were made into the RVLM of urethane-anesthetized rats. 3 Microinjections of ADM decreased the upper plateau, reflex range, and gain, and increased MAP(50), indicating that ADM in the RVLM impairs baroreflex function. 4 ADM(22-52), a putative ADM receptor antagonist, significantly increased the baroreflex gain and upper plateau, demonstrating that endogenous ADM tonically inhibits the baroreflex. Coinjections of ADM(22-52) with ADM blocked the ADM-induced baroreflex responses. 5 ADM's effect was abolished with H-89, a protein kinase A (PKA) inhibitor. 6 Our results show that ADM in the RVLM exerts an inhibitory effect on baroreflex activity via an ADM receptor-mediated mechanism, and that activation of PKA is involved in this event.
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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".