Contribution of T‐type Ca2+ channels to blood pressure regulation in genetically hypertensive rats
Bibliographic record
Abstract
L‐type Ca 2+ channels (LCC) play a major role in Ca 2+ influx into smooth muscle cells and cardiac myocytes. However, other Ca 2+ channels have been recognized to operate in the cardiovascular system of which the T‐type Ca 2+ channels (TCC) have been the focus of attention. Using a novel, highly selective TCC blocker we aimed to determine the contribution of TCC vs. LCC to blood pressure regulation in conscious SHR. Vehicle and equipotent doses of various calcium channels blockers were given IV for 24h. Mibefradil (0.25 mg/kg.h), Amlodipine (0.1 mg/kg.h), Verapamil (0.66 mg/kg.h), and Diltiazem (0.66 mg/kg.h) significantly lowered mean blood pressure (MBP) over 24h by −24±3, −20±4, −22±3, and −22±2 mmHg, respectively and caused tachycardia (5–15%), except Mibefradil. The TCC antagonist (T‐and L‐type IC 50 : 14 and 823 nM), given at 2.95 mg/kg.h IV lowered MBP transiently by −18 mmHg for 1–2h only without changing heart rate. Unbound plasma levels of the novel TCC blocker in vivo were almost 2 times the T‐type IC 50 and 0.03 times the L‐type IC 50 determined in vitro suggesting that the majority of TCC were blocked over 24h. Our studies suggest that the pharmacological effects of the calcium channel blockers tested, including Mibefradil, are due mostly to inhibition of L‐type Ca 2+ channels and that inhibition of T‐type Ca 2+ channels causes acute, transient decreases in blood pressure in conscious genetically hypertensive rats.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".