Sharma J N, Abbas S A
Department of Applied Therapeutics, Faculty of Pharmacy, Health Sciences Center, Kuwait University, Safat, Kuwait.
Methods Find Exp Clin Pharmacol. 2006 May;28(4):217-21. doi: 10.1358/mf.2006.28.4.990204.
In the present investigation, we evaluated the potential effects of captopril, an angiotensin-converting enzyme inhibitor, in the absence and presence of kinin B(2) receptor antagonist (D-Arg-[Hyp3-D-Phe7]-BK) on the duration of survival after prolonged coronary artery ligation in spontaneously hypertensive rats (SHR). The captopril treatment (16 and 32 microg/kg; i.v.) resulted in a significant (p < 0.05) increase in survival time of SHR when compared with that of saline-treated control SHR. Kinin B(2) receptor antagonist (4 microg/kg; i.v.) pretreatment abolished (p > 0.05) the beneficial effect of captopril on the survival time when compared with that in saline-treated control SHR. Both the ligation of coronary artery and captopril treatment resulted in a significant (p < 0.001) fall in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) of SHR when compared with those of the saline-treated control SHR. In addition, captopril administration caused a significant (p < 0.05) fall in SBP, DBP, and HR of SHR before ligation of the coronary artery (preligation). However, there was no significant change (p > 0.05) in SBP, DBP, and HR between saline- and kinin B(2) receptor antagonist plus captopril-treated SHR during preligation. These finding might indicate that captopril possesses a cardioprotective property as demonstrated by an increase in the survival time of SHR. This beneficial effect of captopril is mediated via the kinin B(2) receptor pathway because kinin B(2) receptor antagonist pretreatment blocked the captopril-induced increase in the survival time of SHR.
在本研究中,我们评估了血管紧张素转换酶抑制剂卡托普利在不存在和存在缓激肽B₂受体拮抗剂(D-Arg-[Hyp³-D-Phe⁷]-BK)的情况下,对自发性高血压大鼠(SHR)冠状动脉长期结扎后存活时间的潜在影响。与生理盐水处理的对照SHR相比,卡托普利治疗(16和32微克/千克;静脉注射)使SHR的存活时间显著(p<0.05)增加。与生理盐水处理的对照SHR相比,缓激肽B₂受体拮抗剂(4微克/千克;静脉注射)预处理消除了(p>0.05)卡托普利对存活时间的有益影响。与生理盐水处理的对照SHR相比,冠状动脉结扎和卡托普利治疗均导致SHR的收缩压(SBP)、舒张压(DBP)和心率(HR)显著(p<0.001)下降。此外,在冠状动脉结扎前(结扎前)给予卡托普利导致SHR的SBP、DBP和HR显著(p<0.05)下降。然而,在结扎前,生理盐水处理的SHR与缓激肽B₂受体拮抗剂加卡托普利处理的SHR之间的SBP、DBP和HR没有显著变化(p>0.05)。这些发现可能表明,卡托普利具有心脏保护特性,如SHR存活时间的增加所证明。卡托普利的这种有益作用是通过缓激肽B₂受体途径介导的,因为缓激肽B₂受体拮抗剂预处理阻断了卡托普利诱导的SHR存活时间的增加。