Systemic and renal haemodynamic effects of the specific kappa opioid receptor agonist, U50488H, during postnatal maturation in conscious lambs
Bibliographic record
Abstract
The present experiments were carried out to investigate the role of κ‐opioids in modulating systemic and renal haemodynamics in conscious, chronically instrumented lambs aged ~one week (n = 10) and six weeks (n = 15). Mean arterial pressure (MAP), mean venous pressure (MVP) and renal blood flow (RBF) were measured for 30 min before (Control) and for 90 min after I.V. administration of U50488H (EC 100 dose, experiment one) or vehicle (experiment two). Heart rate (HR) was calculated from the systolic peaks of the arterial pressure waveforms; renal vascular resistance (RVR) was calculated as (MAP ‐ MVP)/RBF. Responses to U50488H were also tested at 1, 24, 48, 72, and 96 h after administration of the selective κ‐opioid receptor antagonist, GNTI. In one week old lambs, 20 min after administration of U50488H, MAP decreased from 79±4 to 74±3 mmHg, remaining at the same level for the next 30 min. In contrast, at six weeks, MAP increased by 10 min after U50488H from 80±6 to 86±9 mmHg, returning to control by 20 min. There was a marked increase in HR after U50488H from 206±26 to 243±15 and from 126±15 to 169±32 bpm, at one and six weeks, respectively; HR remained elevated for the duration of the experiment in both age groups. These responses to U50488H were abolished by GNTI at 24 – 96 h but not 1 h. There were no significant effects on RVR or RBF after U50488H, before or after GNTI, and no effects of vehicle on any of the measured or calculated variables. These data demonstrate that κ‐opioids modulate resting systemic but not renal haemodynamics early in life, in an age‐dependent manner. Funded by the Canadian Institutes for Health Research.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".