【摘要】 目的 研究CPU-86017在大鼠和家兔间心血管作用的差异;观察CPU-86017对大鼠的中枢作用及其对血管内皮细胞的可能作用。方法iv,icv CPU-86017后,观察大鼠和家兔的血压及ECG。给药前,给药后30min,60min,家兔股静脉取血,每次3mL,置于肝素化试管中,分别测定血浆中NO,NOS,ET及CPU-86017的含量。结果大鼠iv CPU-86017（3mg/kg）对血压和心跳无显著影响;jcv给药出现滞后性低血压反应及早期心率显著减慢。家兔iv　CPU-86017（5mg/kg）,在给药0.30,60min,收缩压（SBP）显著下降,下降幅度分别为35.4％,25.5％,16.8％,舒张压分别下降48.4％,30.5％,21.9％,心率下降6.9％,16.3％和13.2％,NO、NOS、ET与给药前无显著性差异。结论CPU-86017对大鼠和家兔的心血管作用存在差异。CPU-86017对心血管系统的作用有中枢作用的参与,其降压作用与血管内皮作用无明显关系。更多还原

【Abstract】 AIM To investigate the species differences in cardiovascular effects of CPU-86017; to evaluate the central effect of CPU-86017 and potential relation to vascular endothelium. METHOD The blood pressure(BP) and ECG were monitored following administration of CPU-86017 by iv and icv routes. The blood samples withdrawn from the femoral vein 30 min before and 60 min after administration were used for the determination of NO, NOS, ET and the concentration of CPU-86017 by validated HPLC. RESULT CPU-86017 (3 mg/kg) injected by iv route did not produce a significant decrease in blood pressure and heart rate(HR) in rats but by icv route caused a delayed hypotension and HR lowering significantly. In rabbits, CPU-86017 (5 mg/kg) injected by iv route produced a significant lowering of the systolic blood pressure (SBP) by 35. 4, 25. 5 and 16. 8% , the diastolic blood pressure(DBP) by 48. 4, 30. 5 and 21. 9% and HR by 6. 9, 16. 3 and 13. 2% respectively at 0, 30 and 60 min. The NO, NOS and ET did not show significant differences at 30 min and 60 min compared to the preadministration values. CONCLUSION There were species differences in cardiovascular effects of CPU-86017 between rats and rabbits. There was a central mechanism involved in the effect of CPU-86017 on the cardiovascular system. The HR exhibited a higher sensitivity to CPU-86017 than the BP in rats. There is no direct link between the hypotensive effect of CPU-86017 and endothelium.更多还原