Difference in Cardiovascular Activities of CPU-86017 between Rat and Rabbit by iv and icv Routes, and Potential Relation to Endothelium
Zi Wang · Zhongguo yaoke daxue xuebao · 2002
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 The blood samples withdrawn from the femoral vein 30 min before and 60 min after administration were used for the determination of NO, NOS, ET and the concentration of CPU-86017 by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.