The 5-HT7 Receptor Contributes to Increased Hindquarter Blood Flow Caused By Skeletal Muscle Contraction
Bibliographic record
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) at low plasma concentrations reduces blood pressure and dilates some skeletal muscle arterioles in the rat. We hypothesized that the 5-HT7 receptor is essential for both 5-HT-induced changes in blood pressure and skeletal muscle arteriolar function. Male 5-HT7 receptor knock out (KO) rats under isoflurane anesthesia had a higher resting hindquarter vascular resistance [HQVR; mm Hg/ml/min; KO (16.0+2.0) vs WT (10.8+0.6.0), p = 0.04]; this was not observed in females. The reduction in blood pressure and HQVR caused by intravenous infusion of 5-HT (25 μg/kg/min) was attenuated (∼56%) in male and female KO rats vs WT. Left anterior descending (LAD) coronary arterial ligation was used to create a model of impaired hindquarter perfusion and exercise intolerance. The goal was to determine whether heart failure associated skeletal muscle blood flow abnormalities were affected by loss of a functioning 5-HT7 receptor in skeletal muscle vasculature. Transdermal neuromuscular electrical stimulation (NMES) was used to mimic exercise induced contraction of skeletal muscle and increase blood flow in the hindquarters (HQ). Male (M) and female (F) 5-HT7 receptor KO rats had a profoundly reduced ability to increase HQ flow during NMES vs WT (% increase from basal; M WT = 118.0+18.0 vs KO=14.6+7.1%; F WT= 101.0+12.0 vs KO = 7.6+6.0%), observed in sham and LAD rats. In a naive cohort of 5-HT7 WT and KO rats, NMES-induced increases in HQ flow did not occur in 5-HT7 receptor KO rats. The NMES-induced increase in HQ flow was also abolished in the presence of the 5-HT7 receptor antagonist SB269970 in normal Sprague-Dawley rats. Lectin visualization of gastrocnemius muscle microvasculature indicateded that the elevated HQVR at rest in male 5-HT7 receptor KO rats was not due to a reduced microvascular density vs the WT. We conclude that 5-HT acting at least in part via the 5-HT7 receptor may have a larger role in (patho)physiological regulation of the circulation than has been heretofore appreciated.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| 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 | 0.001 |
| 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".