挥发性麻醉剂与猪冠状动脉平滑肌中激动剂诱导的收缩以及培养的永生化血管平滑肌细胞中的钙动员

Ozhan M, Sill J C, Atagunduz P, Martin R, Katusić Z S

Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.

Anesthesiology. 1994 May;80(5):1102-13. doi: 10.1097/00000542-199405000-00019.

BACKGROUND

These experiments addressed four specific questions. Do isoflurane and halothane (0.5-3.0% in the gas phase) inhibit contractions evoked in isolated porcine coronary artery rings (without endothelium) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, and F-? Are contractions evoked by phorbol-activated protein kinase C inhibited by the anesthetics? In a well-characterized vascular smooth muscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin-induced Ca2+ mobilization? Do the anesthetics inhibit intracellular Ca2+ mobilization via facilitated cAMP formation?

METHODS

Tension was measured in rings suspended in organ chambers. Apparent intracellular Ca2+ was estimated in cells using indo-1 and flow cytometry. Cyclic AMP was measured by radioimmunoassay.

RESULTS

At the anesthetic concentrations examined, isoflurane attenuated contractions evoked by serotonin and F- but not those induced by endothelin-1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3 x 10(-5) M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ responses evoked by endothelin 10(-8) M were more resistant to anesthetic inhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol-induced responses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. Neither anesthetic facilitated cAMP formation.

CONCLUSIONS

Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizing agonists--by a cellular action beyond the receptor level--but did not inhibit phorbol activated protein kinase C. Serotonin- and endothelin-induced Ca2+ mobilization was inhibited by isoflurane and halothane--but the mechanism does not depend upon increased cAMP.

背景

这些实验探讨了四个具体问题。异氟烷和氟烷（气相中浓度为0.5 - 3.0%）是否抑制由特定的钙动员激动剂5-羟色胺、内皮素-1和F- 在离体猪冠状动脉环（无内皮）中诱发的收缩？佛波醇激活的蛋白激酶C诱发的收缩是否被麻醉剂抑制？在一个特征明确的血管平滑肌细胞培养模型（A7r5和A10）中，麻醉剂是否减弱5-羟色胺和内皮素诱导的钙动员？麻醉剂是否通过促进环磷酸腺苷（cAMP）形成来抑制细胞内钙动员？

方法

在器官浴槽中悬挂的血管环上测量张力。使用indo-1和流式细胞术在细胞中估算表观细胞内钙。通过放射免疫测定法测量环磷酸腺苷。

结果

在所检测的麻醉剂浓度下，异氟烷减弱了5-羟色胺和F- 诱发的收缩，但未减弱内皮素-1或佛波醇二丁酸酯诱导的收缩。在细胞中，2%的异氟烷使3×10⁻⁵ M 5-羟色胺诱导的钙动员减弱约26%，而10⁻⁸ M内皮素诱发的钙反应对麻醉剂的抑制作用更具抗性。氟烷减弱了5-羟色胺、内皮素和F- 在血管环中诱发的收缩，但对佛波醇诱导的反应无作用。在细胞中，2%的氟烷使5-羟色胺诱导的钙动员抑制约43%，使内皮素诱导的钙动员抑制约31%。两种麻醉剂均未促进环磷酸腺苷形成。