血管活性肽优洛可定对自发性高血压大鼠血流动力学影响及与L-型钙通道关系研究

Effects of vasoactive peptide urocortin on hemodynamics in spontaneous hypertensive rat and its relationship with L-type calcium channel

目的观察血管活性肽优洛可定(urocortin,UCN)对自发性高血压大鼠(SHR)血流动力学、心肌重构的影响与相关机制。方法 UCN(1、3、6μg·kg-1·d-1)每日经尾静脉注射给予,用药2周,观察其对SHR血流动力学的影响。应用全细胞膜片钳记录技术,观察UCN对SHR大鼠左室心肌细胞L-型钙通道的影响。另外,采用流式细胞仪方法测定心肌细胞内荧光钙含量。结果 UCN能明显改善SHR心脏的收缩及舒张功能,明显降低平均动脉压(AMP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)(P<0.01),升高左心室压力最大变化速率(±dp/dtmax)(P<0.01),在高血压大鼠血流动力学方面起明显改善作用。另外,UCN能明显抑制L-型钙通道开放,降低心肌细胞钙通道电流,减少SHR大鼠心肌细胞内荧光钙离子含量,而促肾上腺皮质激素调节因子2型受体(CRF-2R)阻断剂Astressin(AST)可消除UCN的作用。结论 UCN改善血流动力学及治疗高血压的作用可能是通过与CRF-2R结合,并抑制心肌细胞内L-钙离子通道开放及降低钙含量而实现。

Aim To investigate the effects of urocortin （UCN） on hemodynamies and the remodeling of myo- cardium, and its mechanism in spontaneous hypertensive rat （SHR）. Methods UCN （1 μg· kg-1 ·d-1,3 μg· kg-1 ·d-1,6 μg· kg-1 ·d-1） was intravenously injected daily for 2 weeks and its effects on hemodynamics in spontaneous hypertensive rat were observed. The whole-cell patch clamp technique was used to compare the effects of UCN on left myocardial cell＇s L-type calcium channel. The flow cytometry method was used to test the content of fluorescence calcium in myocardium. Results UCN improved the systolic and diastolic function of SHR, obviously decreased the AMP, LVSP, LVEDP （P 〈 0. 01 ）, and increased ＋ dp/dtm.x and - dp/dtm,x （P 〈0. 01 ）, improved the hymodynamics for hypertension in SHR. UCN could inhibit the opening of L-type calcium channel and decrease the e- lectric current of cardiamyocytes （ P 〈 0. 01 ）. Further more, UCN could decrease the contents of fluorescence calcium in SHR myocardium （P 〈 0. 01 ）. However, AST, the corticotropin-regulating receptor＇ s antagonist （CRF2R）, could reverse the UCN＇s inhibitory effects （P 〈 0. 01 ）. Conclusion UCN plays an role in trea- ting hypertension via CRF2 receptor and inhibiting the myocardial calcium channel.