Abstract 419: Central Angiotensin II Increases Circulating Endogenous Ouabain, Arterial Myocyte Na/Ca Exchanger Expression and Blood Pressure via Brain Aldosterone and Mineralocorticoid Receptors
Bibliographic record
Abstract
The brain, together with altered arterial function, plays a crucial role in the pathogenesis of hypertension. We have suggested that endogenous ouabain (EO), and its actions on arterial Na + and Ca 2+ transporters, are key in some forms of hypertension; these entities may be controlled by brain mechanisms (review: Blaustein et al., Am J Physiol Heart Circ Physiol 302: H1031-49, 2012). One commonly-used hypertension model involves infusion of angiotensin II (Ang II) in rodents. When Ang II was infused (subcutaneous minipump, 400 ng/kg/min x 15 days) into 8 normal ∼35 g C57Bl/6 mice, 24 hr mean blood pressure (MBP in mm Hg, telemetry), was 119±4, vs 97±2 in 8 vehicle-infused controls, C ( P <0.001). Expression of Na/Ca exchanger-1 (NCX1, immunoblots with R3F1 antibody) was increased by 171±21% ( P <0.001 vs C ) in the aortas of the Ang II-treated mice. To test the role of the brain in Ang II-induced hypertension, vehicle ( C ; n = 7) or Ang II ( A ; n = 8) was administered by intra-cerebroventricular infusion (Ang II, 3.6 μg/day x 12 days) in 200-250 g Wistar rats. In some rats, the Ang II infusion contained the mineralocorticoid receptor (MR) blocker, eplerenone ( E , 5 μg/day x 12 days; n = 7), or the aldosterone synthase inhibitor, FAD-286 ( F , 25 μg/day x 12 days; n = 8). At the end of the treatment, the following MBPs were recorded (mm Hg, telemetry): C : 101±2; A : 123±4 ( P <0.05 vs C, E & F ); E : 108±2; F : 112±2 ( P <0.05 vs C ). Upon euthanasia, blood, pituitary and adrenal samples were taken for EO radioimmunoassay (RIA), and aortas were harvested for NCX1 immunoblotting. The following results were obtained: 1) Plasma EO (nM): C , 0.34±0.07; A , 0.58±0.08 ( P <0.05 vs C ; P <0.01 vs F ); E , 0.37±0.08; F , 0.30±0.05. The plasma EO increase in A was confirmed by off-line liquid chromatography-RIA on pooled samples. 2) NCX1 expression (normalized to C = 1.0±0.2): A , 2.6±0.3 ( P <0.01 vs C ; P <0.05 vs E ); E , 0.9±0.3; F , 1.3±0.2. 3) Adrenal and pituitary EO were not changed. These results provide the first evidence that circulating EO levels and arterial NCX expression are regulated by the brain Ang II-aldosterone-MR system. Thus, in addition to regulating BP by direct, neurally-mediated vasoconstriction, the brain also influences BP by modulating ion transport pathways involved in arterial Na + and Ca 2+ homeostasis.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".