Augmented myogenic constriction in the SHR pre‐glomerular renal arteries protects the kidneys from elevated blood pressure
Bibliographic record
Abstract
Background Spontaneously Hypertensive Rats (SHR) have chronically elevated blood pressures (BPs) at 30 weeks of age (systolic: 191.0 ± 1.0, diastolic: 128.8 ±0.9). However, despite this chronic malignant hypertension, SHR kidneys remain relatively free of pathology and do not display significant proteinuria, due to having an augmented myogenic constriction (MC) in their kidneys [1–2]. In contrast to the SHR, high‐salt fed Dahl Salt Sensitive (DSS) rats have lower BPs (systolic: 163.2 ± 1.4, diastolic: 119.4 ± 1.1), yet show extensive renal pathology, proteinuria, and blunted myogenic response (MR) in the pre‐glomerular vessels. We hypothesize that augmented MC in the SHR pre‐glomerular vessels is due to prostanoid synthesis, providing renal protection. Methods/Results To investigate this hypothesis, we used the inhibitor of prostaglandin H2 synthesis, indomethacin, in the SHR and WKY pre‐glomerular arteries. We also utilized N omega‐nitro‐L‐arginine (LNNA) to examine the effect of nitric oxide blockade on MC, and nifedipine to determine the dependence of MR on L‐type calcium channels. Further, we used a second vascular bed, the mesenteric arcades, to assess the effects of these modulators on myogenic tone. The results showed an enhanced MR in the SHR pre‐glomerular vessels compared to the WKY. Indomethacin attenuated MC in both WKY and SHR renal arteries and nifedipine completely blocked this response in both WKY and SHR pre‐glomerular vessels. In mesenteric arteries, indomethacin decreased MR at high intraluminal pressures in the WKY, and lower pressures in the SHR. LNNA did not change MR in either WKY or SHR, while nifedipine inhibited MC in both WKY and SHR vessels. Conclusions SHR pre‐glomerular arteries show an augmented MC compared to WKY vessels. Prostaglandin increases MC in both WKY and SHR renal arteries. In mesenteric arteries, prostaglandin increases MC at high intraluminal pressures in WKY, but lower pressures in the SHR. Nitric oxide does not affect MR in mesenteric arteries, but L‐type calcium channels play a key role in this response in both renal and mesenteric vessels. Support or Funding Information This work was supported by Canadian Institutes of Health Research grants to Dr. Jeffrey G. Dickhout (PJT148499). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 | 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 | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".