前列腺素H2作为一种内皮源性收缩因子，可调节内皮素-1诱导的收缩。

Prostaglandin H2 as an endothelium-derived contracting factor modulates endothelin-1-induced contraction.

作者信息

Asano H, Shimizu K, Muramatsu M, Iwama Y, Toki Y, Miyazaki Y, Okumura K, Hashimoto H, Ito T

机构信息

Department of Internal Medicine II, Nagoya University School of Medicine, Japan.

出版信息

J Hypertens. 1994 Apr;12(4):383-90.

PMID:8064162

Abstract

OBJECTIVE

To investigate the possible involvement of prostaglandin H2, an endothelium-derived contracting factor in the rat aorta, in the development of the contraction induced by endothelin-1.

METHODS

The aortic rings from spontaneously hypertensive rats (SHR) were prepared, and the changes of isometric tension of these rings developed by endothelin-1 were recorded with or without the treatment of several inhibitors or an antagonist. The concentrations of prostaglandins and thromboxane B2 in the bath solution with the rings contracted by endothelin-1 were measured by radioimmunoassay. The effects of a thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) on endothelin-1-induced contraction were compared in SHR and Wistar-Kyoto (WKY) rats.

RESULTS

Indomethacin (10(-5) mol/l) and ONO-3708 (10(-6) mol/l) significantly diminished endothelin-1 (3 x 10(-8) mol/l)-induced contractions in the aortic rings from SHR with but not without endothelium. The thromboxane A2 synthetase inhibitors OKY-046 (10(-5) mol/l) and RS-5186 (10(-5) mol/l) did not attenuate the contractions either with or without endothelium. Endothelin-1 significantly increased the release of 6-keto-prostaglandin F1 alpha, which is the metabolite of prostaglandin I2 and its precursor prostaglandin H2, from rings with endothelium of SHR, but the concentration of thromboxane B2 from aortic rings was unchanged. In the rings without endothelium the endothelin-1-induced release of 6-keto-prostaglandin F1 alpha was also observed. The half-maximal effective concentration of endothelin-1 for rings from SHR was shifted to the right by ONO-3708, but that of WKY rats was not changed, and significantly greater amounts of 6-keto-prostaglandin F1 alpha were released in the rings from SHR than in those from WKY rats by endothelin-1.

CONCLUSIONS

Endothelin-1 induced the release of prostaglandin H2 from endothelial cells in the rat aorta, the effect being greater in the hypertensive state. The released prostaglandin H2, an endothelium-derived contracting factor, modulated the vasoconstriction that is induced by endothelin-1, another endothelium-derived contracting factor, in addition to the direct vasoconstrictive action of endothelin-1 on vascular smooth muscle.

摘要

目的

研究内皮素-1诱导的大鼠主动脉收缩过程中，内皮衍生收缩因子前列腺素H2可能发挥的作用。

方法

制备自发性高血压大鼠（SHR）的主动脉环，记录在给予或不给予几种抑制剂或拮抗剂处理的情况下，内皮素-1引起的这些主动脉环等长张力的变化。采用放射免疫分析法测定内皮素-1收缩主动脉环的浴槽溶液中前列腺素和血栓素B2的浓度。比较血栓素A2/前列腺素H2受体拮抗剂（ONO-3708）对SHR和Wistar-Kyoto（WKY）大鼠内皮素-1诱导收缩的影响。

结果

吲哚美辛（10⁻⁵ mol/L）和ONO-3708（10⁻⁶ mol/L）能显著减弱内皮素-1（3×10⁻⁸ mol/L）对SHR有内皮主动脉环的收缩作用，而对无内皮主动脉环无此作用。血栓素A2合成酶抑制剂OKY-046（10⁻⁵ mol/L）和RS-5186（10⁻⁵ mol/L）无论有无内皮均不能减弱收缩作用。内皮素-1能显著增加SHR有内皮主动脉环中6-酮-前列腺素F1α的释放，6-酮-前列腺素F1α是前列腺素I2及其前体前列腺素H2的代谢产物，但主动脉环中血栓素B2的浓度未改变。在无内皮的主动脉环中也观察到内皮素-1诱导的6-酮-前列腺素F1α释放。ONO-3708使SHR主动脉环内皮素-1的半数最大效应浓度右移，但对WKY大鼠无此作用，且内皮素-1使SHR主动脉环释放的6-酮-前列腺素F1α量显著多于WKY大鼠。