Human coagulation factor XII-related "new pressor protein": role of PACAP in its cardiovascular and sympathoadrenal effects.
Bibliographic record
Abstract
OBJECTIVE: To investigate the role of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and -27 as possible mediators of the actions of "new pressor protein" (NPP), which is related to coagulation factor XIIa, on blood pressure (systolic and diastolic blood pressure) and heart rate, and on the release of adrenal medullary catecholamines. METHODS: Adult male Wistar bioassay rats (n=8 to 18 per group) were anesthetized with inactin (100 mg/kg intraperitoneally), ganglion-blocked with pentolinium (19.2 mg/kg subcutaneously) and treated with captopril (2.5 mg/kg intravenously). Human NPP was injected at 20 L plasma equivalent per approximately 300 g of rat intravenously, and both PACAPs were injected at 10 g/kg intravenously. The systolic and diastolic blood pressure and heart rate responses to all of these agonists were determined using a MacLab/8 system. Arterial plasma adrenaline and noradrenaline were determined by high performance liquid chromatography with fluorimetric detection. Responses to NPP, the PACAPs and a specific PACAP antagonist were compared to assess the PACAPs as potential mediators of the cardiovascular effects of NPP. RESULTS: PACAP-38 mimicked the effects of NPP on systolic and diastolic blood pressure and heart rate more closely than did PACAP-27. Generally, NPP raised diastolic blood pressure and heart rate, and especially plasma adrenaline and noradrenaline, more impressively in degree and duration than that achieved by the PACAPs. The antagonism of PACAP receptors (PAC-1) significantly reduced the cardiovascular effects of NPP by 30% to 50%. CONCLUSIONS: PACAP-38, especially, may qualify as a potential mediator of the cardiovascular and sympathoadrenal effects of NPP but incomplete inhibition of NPP activity by PAC-1 receptor antagonism and the observed differences all suggest that PACAP is not the only peptide involved. Such peptidic mediation of the effects of NPP may explain the potentiation of NPP by captopril and why NPP remains effective after cholinergic blockade. These data suggest that PACAP is involved in a novel axis between NPP, cardiac function and blood pressure that resists angiotensin-converting enzyme inhibition. Any endogenous production of NPP could raise clinically relevant issues pertaining to therapy with ACE inhibitors.
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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 | 0.000 |
| 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".