The α1-Na/K Pump does not Mediate the Involvement of Ouabain in the Development of Hypertension in Rats
Bibliographic record
Abstract
The Na/K pump of vascular smooth muscle cells (VSMC) and renal epithelial cells (REC) is viewed as a target of digitalis and endogenous ouabain (EO), leading to the development of hypertension. In this study, we compared the effect of ouabain on Na/K pump activity and the intracellular content of monovalent cations in VSMC and REC obtained from rats, humans and dogs. In VSMC from the rat aorta, ouabain inhibited maximal Na/K pump activity measured as the rate of 86Rb influx in Na+-loaded cells, with an ID50 of approximately 20-30 microM without any differences between two strains of normotensive rats (WKY and BN.1x) and three substrains of spontaneously hypertensive rats (SHR). Half-maximal inhibition of the Na/K pump in REC from the rat inner medullary collecting duct was observed at approximately 20 microM of ouabain. In contrast to rat cells, half-maximal inhibition of 86Rb influx in VSMC from human coronary arteries and in REC from the Madin-Darby canine kidney was seen at approximately 0.03 and 0.1 microM ouabain, respectively. At concentrations lower than 100 microM, ouabain did not affect the intracellular content of exchangeable Na+ and K+ in rat VSMC, measured as the steady-state distribution of 22Na and 86Rb, whereas in human VSMC, it increased the intracellular Na+/K+ ratio with an ID50 of approximately 0.5 microM. Keeping in mind that the circulating level of administered digitalis and EO does not exceed 10(-9) M, our results strongly suggest that the involvement of these compounds in the pathogenesis of hypertension in rats is not mediated by inhibition of the alpha1-isoform of the Na/K pump in VSMC and REC. Alternative mechanisms of the involvement of EO and ouabain-like factors in the development of hypertension are considered.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".