Mechanisms of endothelium-dependent vasodilation in male and female, young and aged offspring born growth restricted
Bibliographic record
Abstract
Numerous epidemiological studies have shown that cardiovascular dysfunction in adult life may be programmed by compromised growth in utero. Aging is a risk factor for vascular endothelial-dependent dysfunction. After birth, the impact of intrauterine growth restriction (IUGR) on normal aging mechanisms of vascular dysfunction is not known. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of endothelium-dependent vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (12% O(2)) or control (room air, 21% O(2)) environment from days 15 to 21 of the pregnancy, and both male and female offspring were investigated at 4 or 12 mo of age. Endothelial function was assessed in small mesenteric arteries using methacholine (MCh)-induced vasodilation in a wire myograph system. The involvement of nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) was assessed using the inhibitors N(omega)-nitro-l-arginine methyl ester hydrochloride, meclofenamate, or a combination of apamin and TRAM-34 (SK(Ca) and IK(Ca) blockers), respectively. EDHF-induced vasodilation was further investigated by using inhibitors of P450 epoxygenases [N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide] and gap junctions (18alpha-glycyrrhetinic acid). NO-mediated vasodilation was significantly reduced in aged controls and both young and aged IUGR females. EDHF-mediated vasodilation was maintained in all groups; however, an additional involvement of gap junctions was found in females exposed to hypoxia in utero, which may represent a compensatory mechanism. A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to adult cardiovascular diseases.
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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) | 0.001 | 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) | 0.000 | 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".