Effects of the Loop Diuretic Furosemide on Renal Hemodynamics and Synchronization Among Nearby Nephrons
Bibliographic record
Abstract
Background: Autoregulation of renal blood flow (RBF) among nearby nephrons is presumably synchronized via tubuloglomerular feedback (TGF). TGF controls macula densa solute delivery by adjusting afferent arteriolar diameter and thereby single nephron GFR. As high doses of the diuretic furosemide impair TGF via inhibition of NKCC2 transporters and thus macula densa sodium sensing, we hypothesized that deactivating TGF with furosemide would impair nephron synchronization. Methods: Mean arterial pressure, RBF, urine flow and GFR were measured in anesthetized rats (300-400 g). Left kidney cortical perfusion was recorded using laser speckle imaging, to assess surface perfusion and TGF-mediated nephron synchronization. After baseline, furosemide was infused (10, 20 or 30 mg/kg; n=8) to inhibit TGF. Mean phase coherence (PC), which assesses the degree of phase-locking (synchronization) among multiple oscillators (TGF-driven rhythmic changes of multiple afferent arterioles resistance), the magnitude of decay of TGF PC and length constant associated with initial decay of TGF PC were used to assess strength of synchronization among nephrons. Results: Furosemide did not change MAP (101±10 to 105±39 mmHg, NS) or RBF (7.1±2.3 to 6.9±2.5 ml/min, NS). Right kidney GFR increased after furosemide (1.10±0.22 to 1.27±0.27 ml/min, p<0.05), while left kidney GFR was slightly reduced (1.06±0.22 to 0.92±0.16 ml/min, p<0.05). Furosemide strongly increased right (8±5 to 134±18 uL/min, p<0.001) and left (10±3 to 124±16 uL/min, p<0.001) urine flow. Furosemide decreased the magnitude of the decay of TGF PC (0.46±0.06 to 0.42±0.06, P<0.05) and length constant associated with initial decay of TGF PC (-0.28±0.11 to -0.53±0.06, P<0.001). Furosemide did not affect average PC. Correlation analysis of urine flow, RVR and GFR with parameters of synchronization did not reveal any further support for a decrease in synchronization after furosemide. Conclusions: High dose furosemide decreased the magnitude of decay of TGF PC and length constant associated with initial decay of TGF PC. This indicates weaker synchronization among nephrons within lobules. However, the absence of a change in mean PC makes it likely that mechanisms other than the TGF sensing step in the macula densa differentially affect synchronization amongst nephrons. Funding: Government Support - Non-U.S.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".