5-HT_(1B)受体增强野百合碱诱导的肺性高血压大鼠的肺血管对5-HT收缩反应(英文)

目的:研究肺动脉高压大鼠5-羟色胺引起的肺血管收缩反应及其与5-HT_(1B~-),5HT_(1D~-)受体的关系。方法:应用野百合碱(MCT)诱导的大鼠慢性肺动脉高压模型,通过离体肺动脉环实验建立5-HT的浓度-反应曲线,采用RT-PCR技术检测大鼠肺血管5-HT_(1B~-),5HT_(1D~-)受体mRNA表达。结果:MCT大鼠对5-羟色胺引起的肺血管收缩反应明显增强(E_(max)由38％±21％增加到50％±20％,P<0.05),肺动脉高压大鼠肺血管的5-HT_(1B~-)受体mRNA表达明显明显增多,MCT大鼠肺动脉5-HT_(1B)受体mRNA相对表达比从0.43±0.14增加到0.27±0.15(P<0.05)。结论:肺血管收缩与5-HT_(1B)受体有关,MCT大鼠肺动脉5-HT_(1B~-)受体mRNA表达水平增多与其对5-HT引起的收缩反应增强有关,提示5-HT_(1B)受体有可能成为治疗肺动脉高压的新靶点。

5-HT_1B receptor augmented 5-HT vasoconstrictor response of pulmonary artery in monocrotaline-induced pulmonary hypertensive rats

AIM: To study the relationship between the vasoconstrictor effect to 5-hydroxytryptamine (5-HT) and the expression of 5-HT1B-and 5-HT1D)-receptors in pulmonary arteries (PA) from normal and pulmonary hypertensive (PHT) rats. METHODS: Monocrotaline (MCT)-treated rats were used as a model for chronic PHT. Concentration-response curves of 5-HT induced pulmonary vasoconstriction were established and semiquantitative RT-PCR was performed to identify mRNA expression of 5-HT1B- and 5-HT1D-receptors in rat PA. RESULTS: 5-HT induced vasoconstrictor response of PA from MCT rats was enhanced (Emax) 50 % +/- 20 % vs control 38 % +/- 21 %, P < 0.05). A significantly higher level of 5 -HT1B receptor mRNA expression was detected in PA from MCT rats. The ratio of the PCR products of 5-HT1B receptor gene to those of beta-actin gene was much higher in MCT rats than that in control rats (0.43 +/- 0.14 vs control 0.27 +/- 0.15, P < 0.05). CONCLUSION: 5-HT1B receptor is involved in pulmonary vasoconstriction and the enhanced level of 5-HT1B receptor mRNA expression is closely related to the augmentation of 5-HT induced pulmonary vasoconstriction in PHT rats.