Vascular abnormalities of cerebral arteries and penetrating arterioles during hypertension and heart failure
Bibliographic record
Abstract
Hypertension increases resistance to blood flow and compromises the vasculature. Chronically elevated blood pressure is antecedent to heart failure and both are associated with the development of cognitive decline and dementia. Thus, we sought to examine the cerebrovascular effects of hypertension alone and with predisposition for heart failure. Using pressurized cerebral vessels isolated from animals with genetic hypertension, we investigated structural, mechanical and functional properties by pressure myography. Structural and mechanical parameters were calculated using media and lumen dimensions measured at constant or incremental intraluminal pressures, respectively. Middle cerebral arteries (MCA) from spontaneously hypertensive heart failure (SHHF) rats underwent a combination of growth and remodeling, exhibited greater wall component stiffness and were less compliant. Studies suggest resveratrol may be beneficial for the treatment of hypertension. Therefore, we investigated the effects of resveratrol and two structural analogs on abnormal MCA. Vascular hypertrophy and wall component stiffness improved with oral doses (2.5 mg/kg/d) of resveratrol, pterostilbene and gnetol, albeit in the absence of blood pressure lowering. This indicates these stilbenoids act directly on the vascular wall. Findings in MCA led to further examination of downstream penetrating arterioles that regulate cerebral perfusion. SHHF penetrating arterioles exhibited eutrophic remodeling, increased stiffness and reduced compliance. Although eutrophic remodeling was similarly observed in spontaneously hypertensive rats (SHR), penetrating arterioles were less stiff and more compliant. Transmission electron microscopy revealed increased collagen deposition in arterioles from SHHF rats consistent with reduced compliance. Whereas, SHR arterioles had unchanged collagen/elastin ratio. Functional responses were evaluated using pharmacological agents that were bath applied to penetrating arterioles in increasing concentrations. Relaxation to glutamate/D-serine was reduced in SHHF rats but not in SHR. In contrast, acetylcholine-mediated relaxation was potentiated in SHR but maintained in SHHF rats. Interestingly, endothelium-independent relaxation to nitric oxide donor, sodium nitroprusside, resulted in constriction in both hypertensive strains. These findings suggest penetrating arterioles undergo some adaptations in hypertension, which are absent when there is a propensity for developing heart failure. Altogether, this is the first to identify and characterize the cerebrovascular abnormalities in MCA and penetrating arterioles in models of hypertension alone and with risk for heart failure.
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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".