Inhibitors of Na+/Mg2+ exchange activity attenuate the development of hypertension in angiotensin II-induced hypertensive rats
Bibliographic record
Abstract
Objectives To investigate whether imipramine and quinidine, inhibitors of the Na+/Mg2+ exchanger, influence development of hypertension in rats infused with angiotensin (Ang) II. Methods Sprague–Dawley rats were divided into six groups: (1) control (vehicle); (2) Ang II (150 ng/kg per min subcutaneously); (3) imipramine alone (5 mg/kg per day in drinking water); (4) quinidine alone (5 mg/kg per day in drinking water); (5) Ang II plus imipramine; (6) Ang II plus quinidine. Rats were studied for 3 weeks. To verify that Ang II directly influences Na+-dependent Mg2+ exchange, in-vitro studies were performed in vascular smooth muscle cells (VSMCs) derived from mesenteric arteries. Results Ang II increased systolic blood pressure (SBP) in all groups. The magnitude of the increase was lower (P< 0.01) in Ang II groups treated with imipramine (151 ± 7.4 mmHg) or quinidine (163 ± 4 mmHg) than in the Ang II only group (205 ± 4 mmHg). Neither imipramine nor quinidine influenced SBP in vehicle-treated rats. Plasma concentrations of Mg2+ and K+ were decreased in Ang II rats compared with controls (P< 0.05). Platelet intracellular free Mg2+ concentration was reduced and platelet intracellular free Na+ concentration was increased in the Ang II group compared with control and treated groups (P< 0.01). These effects were normalized by imipramine and quinidine. Ang II stimulated Na+-dependent Mg2+ transport in VSMCs. These actions were abrogated by imipramine and quinidine and in Na+-free conditions. Conclusions Our data demonstrate that inhibitors of Na+-dependent Mg2+ transport attenuate development of hypertension in rats infused with Ang II. These findings suggest a possible role for Na+/Mg2+ exchange activity in the pathogenesis of Ang II-dependent hypertension.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".