Adrenomedullary catecholamine, pressor and chronotropic responses to human coagulation β-FXIIa mediated by endogenous kinins
Bibliographic record
Abstract
OBJECTIVES: There is increasing evidence that blood coagulation factors can influence blood pressure. In the present study, we tested the hypothesis that the beta fragment of human coagulation factor XIIa (beta-FXIIa) induces adrenal catecholamine-mediated pressor and chronotropic responses via bradykinin generated from the plasma kallikrein-kinin system. METHODS AND RESULTS: In anaesthetized bioassay rats with blocked autonomic reflexes, in the Brown Norway strain a bolus injection of beta-FXIIa (1 microg/kg, administered intravenously) elicited a 170-fold rise in plasma epinephrine (from 0.12 +/- 0.02 to 20.58 +/- 2.42 nmol/l; P < 0.001) and a fivefold increase in plasma norepinephrine (from 0.11 +/- 0.02 to 0.57 +/- 0.09 nmol/l; P < 0.01), concurrent increases in systolic blood pressure (from 70 +/- 5 to 101 +/- 4 mmHg; P < 0.01) and heart rate (from 315 +/- 11 to 408 +/- 15 bpm; P < 0.01), and a doubling of bradykinin concentrations (P < 0.05). Bilateral adrenal medullectomy abolished both the catecholamine and the haemodynamic responses to beta-FXIIa. Catecholamine, bradykinin and haemodynamic responses to beta-FXIIa were absent in plasma kininogen-deficient Brown Norway Katholiek (BNK) rats. Exogenous bradykinin dose-dependently reproduced these catecholamine and haemodynamic responses in Brown Norway and BNK rats, but not in Brown Norway adrenal medullectomized rats. CONCLUSION: The pressor and chronotropic responses to beta-FXIIa in this bioassay preparation are mediated exclusively through adrenal catecholamine release, and require plasma kininogens for their full expression. These observations suggest that interaction between the coagulation, kallikrein-kinin and sympatho-adrenal systems can exert important pressor effects in the absence of counterregulatory autonomic reflexes.
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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".