Estrogen and Neuronal Nitric Oxide‐Mediated Inhibition of Sympathetic Vasoconstriction
Bibliographic record
Abstract
Estrogen deficiency has been shown to impair contraction‐mediated inhibition of sympathetic vasoconstriction (sympatholysis) and to reduce skeletal muscle neuronal nitric oxide (NO) synthase (nNOS) expression. Therefore, it has been suggested that estrogen deficiency impairs nNOS‐dependent sympatholysis. However, the effect of estrogen status on NOS‐isoform specific sympatholysis has not been directly investigated with selective pharmacology. The purpose of this study was to investigate the hypothesis that estrogen deficiency impairs nNOS mediated sympatholysis and that estrogen replacement restores sympatholysis through an nNOS dependent mechanism. Female Sprague‐Dawley rats were randomly assigned to ovary‐intact (OI; n=10), ovariectomized (OVX; n=8), and estrogen supplemented OVX (OVX‐E; n=13) groups. OVX rats underwent a bilateral ovariectomy and implantation of either a placebo (OVX) or a time‐release 17β‐estradiol (OVX‐E) pellet. Ten weeks later, rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral vascular conductance (FVC) and stimulation of the lumbar sympathetic chain. The percentage change of FVC (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction in control, selective nNOS inhibition (SMTC; 0.6 mg·kg −1 IV), and non‐selective NOS inhibition (L‐NAME; 10 mg·kg −1 IV) conditions. Resting sympathetic vasoconstrictor responsiveness was not different (p>0.05) between groups and selective nNOS inhibition did not alter (p>0.05) resting sympathetic vasoconstrictor responsiveness in any group. Subsequent non‐selective NOS inhibition augmented (p<0.05) resting vasoconstrictor responses evoked at 2Hz in OI rats, but did not increase sympathetic vasoconstrictor responsiveness in OVX and OVX‐E rats. Vasoconstrictor responses evoked at 5Hz were augmented following non‐selective NOS inhibition (p<0.05; main effect of drug); however, constrictor responses were not different between groups. In contracting muscle, sympathetic vasoconstrictor responsiveness was similar (p>0.05) between groups and selective nNOS blockade did not alter (p>0.05) sympathetic vasoconstrictor responsiveness in OI, OVX or OVX‐E rats. Non‐selective NOS inhibition augmented (p<0.05) vasoconstrictor responses evoked at 2Hz in OI rats, but not in OVX and OVX‐E rats. Non‐selective NOS inhibition increased (p<0.05; main effect of drug) vasoconstrictor responsiveness to sympathetic stimulation delivered at 5Hz; however, constrictor responses were not different between groups. Sympatholysis was similar (p>0.05) in OI (2Hz: 24 ± 9%; 5Hz: 28± 10%), OVX (2Hz: 24 ± 8%; 5Hz: 26 ± 9%) and OXV‐E (2Hz: 29 ± 9%; 5Hz: 32 ± 9%) rats. Selective nNOS inhibition did not alter (p>0.05) sympatholysis. Non‐selective NOS inhibition diminished (p<0.05; main effect of drug) sympatholysis of responses evoked at 5Hz. These data suggest that estrogen status does not modulate sympathetic vasoconstrictor responsiveness in resting or contracting skeletal muscle. Furthermore, NO derived from nNOS does not appear to be necessary for sympatholysis in female rats regardless of estrogen status. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.001 | 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".