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 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 | 0.006 | 0.019 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.007 |
| Bibliometrics | 0.013 | 0.014 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".