Influence of T-type Ca<sup>2+</sup>(mibefradil) and Cl<sup>-</sup>(indanyloxyacetic acid 94) channel antagonists on α<sub>1</sub>-adrenoceptor mediated contractions in rat aorta
Bibliographic record
Abstract
The effects of the T-type and L-type Ca2+channel antagonists, mibefradil and nifedipine, respectively, and those of a Cl-channel antagonist, indanyloxyacetic acid 94, on mechanical responses elicited by selective activation of α1-adrenoceptors using cirazoline were examined in rat isolated aortic rings. The presence of mibefradil (300 nM), indanyloxyacetic acid, 94 (30 µM) and nifedipine (300 nM) alone inhibited mechanical responses elicited by cirazoline. The concentration-response curves to cirazoline were displaced to the right with significant increases in the EC50and significant depressions of the maximal responses in the presence of the individual agents mibefradil, indanyloxyacetic acid 94, or nifedipine. A combination of mibefradil and indanyloxyacetic acid 94 further inhibited the mechanical activity produced by cirazoline. The further reduction in the maximal response to cirazoline, in the presence of mibefradil and nifedipine, was insignificant when compared with the effects of nifedipine alone. In addition, maximal mechanical responses produced by cirazoline were not significantly affected by a combination of nifedipine and indanyloxyacetic acid 94 when compared with either nifedipine alone or mibefradil and indanyloxyacetic acid 94 combined. Our current findings indicate that mibefradil, indanyloxyacetic acid 94, and nifedipine can inhibit cirazoline-induced contractions to a varying degree. Moreover, based on our present data it would be reasonable to suggest that the contribution of T-type versus L-type Ca2+channels to contractile responses obtained with cirazoline are approximately 21% and 35%, respectively, of the Emax. It would appear that L-type Ca2+channels play a greater role in processes that are involved in excitation-contraction coupling subsequent to stimulation of α1-adrenoceptors. In addition, Cl-channels also appear to be involved in the process of contraction following α1-adrenoceptor activation.Key words: T-type Ca2+channels, L-type Ca2+channels, Cl-channels, isolated aortic rings.
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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 | 0.001 |
| 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".