前列腺素I2、E2和D2可能激活离体大鼠心脏中ATP敏感性钾通道的证据。

Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart.

作者信息

Bouchard J F, Dumont E, Lamontagne D

机构信息

Faculté de pharmacie, Université de Montréal, Quebec, Canada.

出版信息

Cardiovasc Res. 1994 Jun;28(6):901-5. doi: 10.1093/cvr/28.6.901.

DOI:10.1093/cvr/28.6.901

PMID:7522966

Abstract

OBJECTIVE

The aim was to study the contribution of ATP sensitive potassium channels (KATP channels) in the coronary vasodilatation produced by prostaglandins I2, E2, and D2 in rats.

METHODS

Isolated Langendorff rat hearts, perfused under constant flow conditions, and rat aortic rings were used. Dose-response curves to PGE2, PGD2, and iloprost, a PGI2 analogue, were performed before and during KATP channel blockade with glibenclamide. Arachidonic acid was used to increase the formation of endogenous PGI2.

RESULTS

Infusions of PGE2, PGD2, and iloprost in isolated hearts induced marked vasodilatation, as reflected by the reduction in coronary perfusion pressure of 27(SEM 7), 30(6), and 43(6)%, for 0.1 microM PGE2, PGD2, and iloprost, respectively. Infusion of glibenclamide (0.3 microM) was accompanied by a 23(3)% increase in coronary perfusion pressure. The vasodilatation induced by levcromakalim (0.1 microM) was completely inhibited in the presence of glibenclamide, whereas that of papaverine (30 microM) was unaffected. Glibenclamide significantly reduced the vasodilatation induced by iloprost (at 3 to 100 nM), PGE2 (30 and 100 nM), and PGD2 (30 and 100 nM), at all concentrations studied. In contrast, glibenclamide (1 microM) had no effect on iloprost induced relaxation of aortic rings. Arachidonic acid infusion (from 0.1 to 3 microM) in isolated hearts induced a pronounced vasodilatation and a significant release of 6-keto-PGF1 alpha into the coronary effluent in a dose dependent fashion. Both responses to arachidonic acid were significantly reduced in the presence of the cyclo-oxygenase inhibitor diclofenac (1 microM). In an additional experimental series, the vasodilatation induced by arachidonic acid infusions was found to be significantly reduced in the presence of glibenclamide.

CONCLUSIONS

Glibenclamide is a potent inhibitor of the coronary dilator action of prostaglandins I2, E2, and D2. This observation suggests that these prostaglandins may cause vasodilatation by opening KATP channels.

摘要

目的

研究三磷酸腺苷敏感性钾通道（KATP通道）在前列腺素I2、E2和D2诱导的大鼠冠状动脉舒张中的作用。

方法

采用恒流条件下灌注的离体Langendorff大鼠心脏和大鼠主动脉环。在用格列本脲阻断KATP通道之前和期间，分别绘制对前列腺素E2、D2和前列环素类似物伊洛前列素的剂量-反应曲线。使用花生四烯酸增加内源性前列环素的生成。

结果

在离体心脏中输注前列腺素E2、D2和伊洛前列素可诱导明显的血管舒张，分别输注0.1微摩尔的前列腺素E2、D2和伊洛前列素后，冠状动脉灌注压分别降低27（标准误7）%、30（6）%和43（6）%。输注格列本脲（0.3微摩尔）后，冠状动脉灌注压升高23（3）%。在存在格列本脲的情况下，左卡尼汀（0.1微摩尔）诱导的血管舒张被完全抑制，而罂粟碱（30微摩尔）诱导的血管舒张不受影响。在所有研究浓度下，格列本脲均显著降低伊洛前列素（3至100纳摩尔）、前列腺素E2（30和100纳摩尔）和前列腺素D2（30和100纳摩尔）诱导的血管舒张。相比之下，格列本脲（1微摩尔）对伊洛前列素诱导的主动脉环舒张无影响。在离体心脏中输注花生四烯酸（0.1至3微摩尔）可诱导明显的血管舒张，并以剂量依赖方式使冠状动脉流出液中6-酮-前列腺素F1α显著释放。在存在环氧化酶抑制剂双氯芬酸（1微摩尔）的情况下，对花生四烯酸的两种反应均显著降低。在另一个实验系列中，发现在存在格列本脲的情况下，花生四烯酸输注诱导产生的血管舒张显著降低。