Prenatal Hypoxia is Associated with Coronary Artery Endothelial Dysfunction in Male and Female Offspring
Bibliographic record
Abstract
Introduction Fetal hypoxia is a common consequence of complicated pregnancies and is linked to the development of cardiovascular (CV) dysfunction in the offspring. We showed an impaired cardiac function in adult prenatal hypoxia offspring, however, the mechanisms are not known. Coronary artery endothelial dysfunction has been shown to contribute to the development of cardiac dysfunction, however, whether endothelial function is impaired in coronary arteries of prenatal hypoxia offspring is unknown. We hypothesize that prenatal hypoxia leads to impaired coronary artery endothelial function in adult male and female offspring. Methods Pregnant Sprague‐Dawley rats were exposed to normoxia (21% O 2 ) or hypoxia (11% O 2 ; p‐Hyp) on gestational days 15‐21 (term=22 days). Male and female offspring were aged to 9‐9.5 months. Left anterior descending coronary arteries were isolated (n=5‐7/group), and endothelium‐dependent vasodilation to methylcholine (MCh) and endothelium‐independent vasodilation to the nitric oxide (NO) donor sodium nitroprusside (SNP) were assessed by wire myography. To assess the contribution of endothelial vasodilation pathways, MCh‐curves were performed in the presence/absence of inhibitors of nitric oxide synthase (L‐NAME), prostaglandin H synthase ([PGHS]; meclofenamate), or small‐ and intermediate‐conductance Ca 2+ ‐activated potassium channels (apamin and TRAM‐34, respectively). Data were summarized as Emax (maximum vasodilation response), pEC 50 (concentration required to produce 50% of Emax) or Area Under the Curve (AUC). Data were compared by two‐way ANOVA (Sidak's post hoc test); p<0.05 was significant. Results Mch‐induced vasodilation (Emax) was decreased in p‐Hyp males (p=0.006) and females (p=0.032) compared to normoxia offspring. L‐NAME completely inhibited vasodilation (AUC) in normoxia and p‐Hyp males (p<0.0001). In the female offspring, incubation with L‐NAME completely inhibited vasodilation in the normoxia group (p<0.0001), but to a lesser extent (Emax ~15%) in the p‐Hyp offspring (p<0.0001). In contrast, meclofenamate did not alter MCh‐induced vasodilation (AUC) in males, while in females, meclofenamate increased vasodilation to MCh in the p‐Hyp group only (p=0.04). Apamin and TRAM‐34 did not alter responses to MCh in any of the groups. SNP sensitivity (pEC 50 ) was decreased in p‐Hyp females compared to normoxia controls (p=0.012), without changes in males. Conclusions Our data suggest that prenatal hypoxia leads to coronary artery endothelial dysfunction in male and female offspring. In prenatal hypoxia males, NO contribution to endothelium‐mediated vasodilation was reduced. In females, prenatal hypoxia increased PGHS‐dependent vasoconstriction and decreased smooth muscle sensitivity to NO. Understanding the mechanistic pathways involved in programming of CV disease may allow for the development of future prenatal and postnatal therapeutic interventions.
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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) | 0.003 | 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".