Angiotensin II/AT2 receptor-induced vasodilation in stroke-prone spontaneously hypertensive rats involves nitric oxide and cGMP-dependent protein kinase
Bibliographic record
Abstract
BACKGROUND: Angiotensin II (Ang II) induces vasodilation, in part, through angiotensin type 2 receptor (AT2R)-induced actions in conditions associated with angiotensin type 1 receptor (AT1R) blockade and AT2R upregulation. Ang II/AT2R-induced vasodilation involves nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-dependent processes. We previously demonstrated that AT2R-mediated effects involve inhibition of the RhoA/Rho kinase pathway. However, molecular mechanisms underlying this phenomenon are unknown. AIMS: In the present in-vivo study we tested the hypothesis that AT2R-elicited vasodilation is associated with nitric oxide synthase (NOS) activation and NO production, and that a cGMP-dependent protein kinase (cGKI), which inactivates RhoA, is upregulated when stroke-prone spontaneously hypertensive rats (SHRSP) are treated with AT1R blockers. METHODS: SHRSP and Wistar-Kyoto (WKY) rats were treated with the AT1R blocker valsartan for 14 days. Dilatory responses to Ang II with or without the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) were performed in norepinephrine-precontracted vessels in the presence of valsartan. Expression of AT2R, endothelial NOS (eNOS) and cGKI was assessed by immunoblotting. NO bioavailability and NAD(P)H oxidase activity were evaluated by chemiluminescence. RESULTS: Ang II elicited vasodilation in valsartan-treated SHRSP. L-NAME inhibited this effect, indicating a role for NO. eNOS expression and NO concentration were increased twofold by valsartan, only in SHRSP. Expression of cGKI was reduced in SHRSP and restored after valsartan treatment. NAD(P)H oxidase activity was approximately threefold higher in SHRSP versus WKY (P < 0.05) and reduced by valsartan. CONCLUSIONS: Ang II, via AT2R, facilitates vasodilation through NOS/NO-mediated pathways and upregulation [corrected] of CGK1 [corrected] after chronic AT1R antagonism. These effects may contribute in part to beneficial actions of AT1R blockers in the treatment of hypertension.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".