Tyrosine Kinase Inhibition Attenuates Vasopressin-induced Contraction of Mesenteric Resistance Arteries: Alterations in Spontaneously Hypertensive Rats
Bibliographic record
Abstract
This study examined the role of tyrosine kinase-dependent signaling pathways in arginine vasopressin (AVP)-induced contractile responses in resistance arteries from spontaneously hypertensive rats (SHR). Systolic blood pressure was measured in conscious 6- and 21-week old SHR and Wistar Kyoto rats (WKY) by tail cuff measurements. Segments of third-order mesenteric arteries (about 200 microm in diameter, 2mm in length) were mounted in a pressurized chamber with the intraluminal pressure maintained at 45 mmHg. Contractile effects of AVP (10-12 to 10-7 mol/l) were determined in the absence and presence of the selective tyrosine kinase inhibitor tyrphostin A23 (10-5 mol/l) and the inactive analogue, tyrphostin A1 (10-5 mol/l). Systolic blood pressure was significantly higher in SHR compared with age-matched WKY (p < 0.01). AVP increased contraction in a dose-dependent manner with significantly greater responses in adult SHR (pD2 = 10.3 +/- 0.06) than age-matched WKY (pD2 = 9.4 +/- 0.04). Tyrphostin A23 shifted the AVP dose response curve to the right in 6- and 21-week WKY and 6-week SHR, but had little effect on AVP-induced responses in 21-week-old SHR. Tyrphostin A1 did not influence contraction in any groups. Protein tyrosine phosphorylation in VSMCs and mesenteric arteries was increased 2-3 fold in 21-week SHR compared with WKY counterparts. AVP significantly increased tyrosine phosphorylation in VSMCs, with enhanced effects in SHR compared with WKY (p < 0.05). These effects were inhibited by tyrphostin A23. Our findings demonstrate that protein tyrosine kinases contribute to AVP-induced contraction of resistance arteries from WKY and SHR during the phase of developing hypertension. These processes do not seem to play an important role in AVP-induced hypercontractility in SHR with established 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 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".