Abbas S A, Sharma J N, Yusof A P
Department of Pharmacology and Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang.
Immunopharmacology. 1999 Oct 15;44(1-2):93-8. doi: 10.1016/s0162-3109(99)00155-1.
It is known that BK does play a role in the cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors. The present study therefore was conducted to examine the effects of bradykinin (BK) and its antagonist on survival time in spontaneously hypertensive rats (SHR) with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure (BP) in the presence and absence of BK and BK2 receptor antagonist, D-Arg-[Hyp-D-Phe7]BK. Coronary artery was ligated in anaesthetized rats and they were artificially ventilated with room air (stroke volume, 4 ml; 48 strokes/min) as described by the previous investigators. Lead II elecrocardiogram (ECG) was recorded from subcutaneous steel needle electrodes. Results of this investigation indicated that BK treatment 4 microg/kg (i.v.) and 8 microg/kg (i.v.) caused significant (P < 0.05) increase in survival time in SHR with coronary artery ligation for 15 min and continuously as compare to their respective saline-treated controls. However, BK antagonist treatment 4 microg/kg (i.v.) abolished the increase in survival time caused by BK treatment. The mean values of survival time between the saline-treated and BK antagonist plus BK-treated rats did not differ significantly (P > 0.05). The heart rate and BP responses were greatly reduced (P < 0.001) in the presence of coronary artery ligation. These findings suggest that BK might have cardioprotective effect to increase the survival time in rats by activating BK2 receptors after coronary artery ligation.
已知缓激肽(BK)在血管紧张素转换酶(ACE)抑制剂的心脏保护作用中确实发挥了作用。因此,本研究旨在检测缓激肽(BK)及其拮抗剂对冠状动脉结扎15分钟并持续结扎的自发性高血压大鼠(SHR)存活时间的影响。我们还评估了在有或没有BK和BK2受体拮抗剂D-Arg-[Hyp-D-Phe7]BK的情况下心率和血压(BP)。按照先前研究者的描述,在麻醉的大鼠中结扎冠状动脉,并使用室内空气进行人工通气(每搏量4 ml;每分钟48次搏动)。通过皮下钢针电极记录II导联心电图(ECG)。本研究结果表明,与各自的生理盐水处理对照组相比,4μg/kg(静脉注射)和8μg/kg(静脉注射)的BK处理使冠状动脉结扎15分钟并持续结扎的SHR的存活时间显著增加(P<0.05)。然而,4μg/kg(静脉注射)的BK拮抗剂处理消除了BK处理导致的存活时间增加。生理盐水处理组与BK拮抗剂加BK处理组大鼠的平均存活时间差异不显著(P>0.05)。在冠状动脉结扎的情况下,心率和血压反应大大降低(P<0.001)。这些发现表明,BK可能通过在冠状动脉结扎后激活BK2受体而具有心脏保护作用,从而增加大鼠的存活时间。