Regulation of Vascular Tone During Pregnancy
Bibliographic record
Abstract
During pregnancy, maternal vascular function is altered through mechanisms that remain unclear. Progesterone synthesis and metabolism are also increased. Progesterone metabolites are potent endogenous ligands for the pregnane X receptor (PXR), a nuclear receptor that induces the expression of hepatic cytochrome P450 enzymes. Cytochrome P450 enzymes located in the vasculature can metabolize arachidonic acid to produce epoxyeicosatrienoic acids, known vasodilators. We hypothesized that PXR is present in vascular tissue and contributes to vascular adaptations to pregnancy. PXR mRNA was detected in mouse mesenteric arteries by quantitative RT-PCR. Constrictor and relaxation responses in wildtype (PXR(+/+)) and PXR-deficient (PXR(-/-)) mice were compared by wire myography. Relative to nonpregnant controls, arteries from pregnant PXR(+/+) mice had reduced sensitivity to phenylephrine-induced constriction (EC(50): 2.77+/-0.32 mumol/L versus 5.13+/-0.36 mumol/L; P=0.009) and enhanced maximal vasorelaxation to bradykinin (26+/-3% versus 44+/-16%; P=0.013). However, these pregnancy adaptations were absent in PXR(-/-) mice. We also hypothesized that PXR is activated by progesterone metabolites. Treatment of PXR(+/+) and PXR(-/-) nonpregnant mice with 5beta-dihydroprogesterone for 7 days enhanced endothelium-dependent relaxation in only the PXR(+/+) mice, similarly to that seen in pregnancy. In treated mice, inhibition of cytochrome P450 epoxygenase activity with N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide attenuated vasorelaxation in arteries from PXR(+/+) but not PXR(-/-) mice. We conclude that PXR contributes to the development of vascular adaptations to pregnancy, likely in response to activation by progesterone metabolites, and that PXR-dependent increases in vasorelaxation may be because of activation of cytochrome P450 epoxygenases.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".