Impaired Dilator Reactivity of Middle Cerebral Arteries in Goto‐Kakizaki Rats with Type II Diabetes Mellitus
Bibliographic record
Abstract
Type II diabetes mellitus (T2DM) is a highly prevalent disease and is associated with the development of cerebrovascular disease. The objective of the study was to determine whether alterations to the regulation of cerebral vascular tone exist in a non‐obese model of T2DM and to determine the mechanistic contributors to changes in this response. Middle cerebral arteries (MCA) from 17–18‐wk‐old male Wistar Kyoto (WKY) and Goto‐Kakizaki (GK) were isolated and cannulated with glass micropipettes. Vascular reactivity was assessed in response to challenge with acetylcholine (ACh), sodium nitroprusside (SNP), reductions in Po 2 , 5‐HT, and increased intraluminal pressure. Vessels were treated with the competitive nitric oxide synthase (NOS) inhibitor L‐NAME, the cyclooxygenase inhibitor indomethacin, and the cell‐permeable superoxide dismutase (SOD) mimetic TEMPOL to support interpretation of mechanistic contributors to changes in vessel reactivity. Similar measurements of vascular reactivity to methacholine (MCh), phenylephrine, SNP, and reductions in PO 2 were measured in aortic ring preparations, along with measurements of vascular NO production and metabolites of arachidonic acid. There was an impairment of vessel dilation within the MCA and aorta of GK in response to ACh/MCh and hypoxia but not SNP. Decreased vascular NO release and ratio of PGI 2 /TxA 2 were measured within the aorta in response to hypoxia, and increasing MCh concentration. No change was seen in the constrictor response to either 5‐HT or phenylephrine within the MCA or aorta respectively or in the myogenic activation of the MCA. Treatment with L‐NAME severely blunted the dilator reactivity of both the MCA and aorta, while TEMPOL showed mild improvements in GK, and indomethacin yielded improved dilator reactivity to MCh in GK but blunted it in WKY. These results suggest that the vasodilator reactivity of the MCA and aorta of GK in response to endothelium‐dependent dilator stimuli is impaired vs. WKY. This may be due to decreased NO bioavailability and altered arachidonic acid metabolism as a result of a pro‐oxidant pro‐inflammatory condition present in T2DM. The lack of change to the constrictor response of MCA and aorta in GK suggests a lack of structural remodeling as a result of T2DM at this age. Support or Funding Information American Heart Association and National Institutes of Health (USA); Canadian Institutes for Health Research and Natural Sciences and Engineering Research Council (Canada) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".