Crosstalk between the heme oxygenase system, aldosterone, and phospholipase C in hypertension
Bibliographic record
Abstract
BACKGROUND: Aldosterone is a mineral corticoid hormone that is produced in response to angiotensin-II, and like angiotensin-II, stimulates inflammation, oxidative stress, and fibrosis by activating nuclear factor-kappaB and activating protein-1. Recent evidence, however, indicates that aldosterone stimulates phospholipase C and activates nuclear factor-kappaB and activating protein-1. Although the heme oxygenase system is cytoprotective, its effects on aldosterone-phospholipase C signaling in deoxycorticosterone acetate (DOCA-salt) hypertension, a model of aldosteronism, and spontaneously hypertensive rat, a genetic model of human essential hypertension, have not been fully characterized. METHODS: In the present study, the heme oxygenase inducer, hemin, was given to spontaneously hypertensive and deoxycorticosterone acetate hypertensive rats, and the effects on blood pressure, aldosterone, nuclear factor-kappaB, activating protein-1, phospholipase C, and inositol 1,4,5-triphosphate were examined. RESULTS: Hemin therapy restored physiological blood pressure to spontaneously hypertensive rats (209.9 +/- 0.9 to 127.3 +/- 0.85 mmHg, n = 10, P < 0.01) and to deoxycorticosterone acetate salt hypertensive rats (195.7 +/- 1.8 vs.132.5 +/- 2.1 mmHg; P < 0.01, n = 10), but had no effect on age-matched normotensive Wistar-Kyoto or Sprague-Dawley strains. The antihypertensive effect was accompanied by enhanced heme oxygenase activity, upregulated cyclic guanosine monophosphate-protein kinase G signaling, increased superoxide dismutase activity, and the potentiation of total antioxidant capacity, whereas aldosterone, activating protein-1, and nuclear factor-kappaB were reduced. Furthermore, hemin suppressed phospholipase C activity, attenuated inositol 1,4,5-triphosphate, and reduced resting intracellular calcium in the aorta. CONCLUSION: Collectively, our results suggest that the concomitant depletion of aldosterone, phospholipase C-inositol 1,4,5-triphosphate activity, resting intracellular calcium and the corresponding decline of inflammatory, and oxidative insults may account for the antihypertensive effects of hemin in deoxycorticosterone acetate hypertension and spontaneously hypertensive rats.
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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 | 0.001 | 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".