Modulation of Human Arterial Tone During Pregnancy: The Effect of the Bioactive Metabolite Sphingosine-1-Phosphate1
Bibliographic record
Abstract
Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that has been implicated in cardiovascular disease. The objective of the present study was to determine the vasoactive effects and underlying mechanisms of S1P on adult human maternal arteries. The isometric tensions of the omental and myometrial arteries isolated from normal pregnant women at term were assessed in response to incremental doses of S1P in the presence or absence of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The putative involvement of Rho-associated kinases (ROCKs) in intact arteries and in those permeabilized with alpha-toxin, to study agonist-dependent calcium-sensitization, was assessed with the inhibitor Y27632. Real-time RT-PCR established the presence of mRNA encoding the S1P receptors (S1P(1) to (3)), previously known as endothelial differentiation gene receptors (EDG1, 3 and 5), in both artery types. S1P induced a dose-dependent increase in the isometric tension of all the arteries. Y27632 reduced constriction due to S1P in intact arteries and reduced S1P-induced sensitization of contraction to submaximal activating Ca(2+) in permeabilized arteries. L-NAME also modulated S1P vasoactive responses in a tissue-specific manner. Two subgroups of omental arteries were identified, one of which utilizes the NO pathway. In myometrial arteries, S1P evoked oscillatory constrictions, whereas pretreatment with L-NAME resulted in only tonic constrictions of unaltered peak magnitude. The prominent vasoactive actions of S1P in the maternal arteries of pregnant women are modulated by inhibitors of ROCKs and NO bioavailability. The subtle tissue-specific functional differences in the modulation of S1P actions by NO have important implications for vascular tone regulation by this bioactive circulatory metabolite during pregnancy.
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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".