Sakamoto J, Miura T, Goto M, Iimura O
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Cardiovasc Res. 1995 May;29(5):682-8.
The aim was to test whether infarct size limitation by adenosine A1 receptor activation is mediated by protein kinase C.
In the first series of experiments, myocardial infarction was induced in rabbits under pentobarbitone anaesthesia by 30 min coronary artery occlusion and 3 h reperfusion. Rabbits were pretreated with no drugs (control). 1 mg.kg-1 of R(-)N6-2-phenylisopropyl adenosine (PIA), 50 micrograms.kg-1 of staurosporine (Stauro), 2.5 mg.kg-1 of polymyxin B (PolyB), and a combination of PIA and either Stauro or PolyB. Infarct size and the area at risk were determined by tetrazolium staining and fluorescent particles, respectively. In the second series of experiments, the inotropic response to 4 beta-phorbol 12-myristate 13-acetate (PMA) was assessed in rabbits with and without pretreatment using the same doses of Stauro and PolyB as those in the first series of experiments.
Infarct size expressed as percent of area at risk (%IS/AR) was significantly smaller in the PIA treated group than in the control: %IS/AR = 19.0(SEM 2.4)% v 37.7(4.0)%, P < 0.05. However, %IS/AR in the groups given Stauro [35.0(4.2)%], PolyB [37.9(3.2)%], PIA plus Stauro [34.9(3.9)%], and PIA plus PolyB [36.3(3.3)%] did not differ from the control value. PMA at the dose of 0.02 and 0.05 micrograms.kg-1 caused a dose dependent increase of the left ventricular dP/dtmax in the untreated rabbits. Such a positive inotropic response to PMA was not detected in rabbits pretreated with Stauro or PolyB, suggesting that the doses of the protein kinase C inhibitors were appropriate to block protein kinase C in the heart.
Infarct size limitation by A1 receptor stimulation is mediated by activation of protein kinase C in pentobarbitone anaesthetised rabbits.
旨在测试腺苷A1受体激活对梗死面积的限制作用是否由蛋白激酶C介导。
在第一系列实验中，对戊巴比妥麻醉下的家兔进行30分钟冠状动脉闭塞和3小时再灌注以诱导心肌梗死。家兔未用药物预处理（对照组）。给予1mg·kg-1的R(-)N6-2-苯基异丙基腺苷（PIA）、50μg·kg-1的星形孢菌素（Stauro）、2.5mg·kg-1的多粘菌素B（PolyB），以及PIA与Stauro或PolyB的组合。分别通过四氮唑染色和荧光颗粒测定梗死面积和危险区面积。在第二系列实验中，使用与第一系列实验相同剂量的Stauro和PolyB，评估预处理和未预处理家兔对4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）的变力反应。
以危险区面积百分比表示的梗死面积（%IS/AR）在PIA治疗组中显著小于对照组：%IS/AR = 19.0（标准误2.4）%对37.7（4.0）%，P < 0.05。然而，给予Stauro [35.0（4.2）%]、PolyB [37.9（3.2）%]、PIA加Stauro [34.9（3.9）%]和PIA加PolyB [36.3（3.3）%]组的%IS/AR与对照值无差异。剂量为0.02和0.05μg·kg-1的PMA导致未处理家兔左心室dP/dtmax呈剂量依赖性增加。在用Stauro或PolyB预处理的家兔中未检测到对PMA的这种正性变力反应，表明蛋白激酶C抑制剂的剂量足以阻断心脏中的蛋白激酶C。
在戊巴比妥麻醉的家兔中，A1受体刺激对梗死面积的限制作用由蛋白激酶C的激活介导。
