Pathophysiological aspects of the interaction between endogenous natriuretic factors and digoxin-like substances as different functional systems of central nervous system regulation: a systematic review
Bibliographic record
Abstract
Background: Endogenous natriuretic factors (ENFs) and digitalis-like substances (DLS) are key endogenous regulators influencing the central nervous system (CNS) through distinct molecular mechanisms. ENFs, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), primarily regulate water-salt balance and vascular tone through guanylate cyclase receptor activation, while DLS, including endogenous ouabain and marinobufagenin, modulate Na-K-ATPase activity, affecting neuronal excitability and intracellular signaling cascades. Objective: To conduct a comprehensive systematic analysis of ENFs and DLS as functionally distinct CNS regulatory systems, evaluating their molecular mechanisms, clinical significance, and therapeutic potential. Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library databases from 1957 to 2025. Search terms included: "endogenous natriuretic factors", "digitalis-like substances", "central nervous system regulation", "Na-K-ATPase inhibition", "ouabain-like compounds", "marinobufagenin". Study selection followed PRISMA 2020 guidelines with independent screening by two reviewers. Quality assessment used Cochrane RoB 2.0 for RCTs and Newcastle-Ottawa Scale for observational studies. Results: From 1,247 identified publications, 89 studies met inclusion criteria (n=15,847 participants). ENFs affect the CNS via cGMP-dependent mechanisms, reducing sympathetic activity by 20-35% and modulating neurotransmission through NPR-A, NPR-B, and NPR-C receptors. DLS activate Src-kinase cascades through selective inhibition of Na-K-ATPase α-subunits, influencing circadian rhythms and cognitive functions. In pathological conditions, characteristic imbalances were observed: DLS levels increased 1.5-2.8-fold in essential hypertension and depression, while ENF activity decreased 25-40% in neurodegenerative diseases. Conclusions: ENFs and DLS function as independent but interconnected regulatory systems with significant therapeutic potential. Understanding their distinct mechanisms opens new avenues for developing personalized treatment strategies for neurological disorders.
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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 | 0.000 | 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 | 0.000 |
| 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".