Shizukuda Y, Buttrick P M, Geenen D L, Borczuk A C, Kitsis R N, Sonnenblick E H
Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Physiol. 1998 Sep;275(3):H961-8. doi: 10.1152/ajpheart.1998.275.3.H961.
To establish whether catecholamines per se in the absence of significant increases in systolic load induce myocardial damage via apoptosis, rats were treated with vehicle or isoproterenol (400 microg . kg-1 . h-1). Apoptotic cardiocytes (Apo) were identified in paraffin-embedded sections using terminal deoxynucleotide transferase-mediated dUTP nick end labeling. Results were confirmed using an independent ligase assay. Systolic blood pressures were comparable in isoproterenol-treated and control rats. Twenty-four hours of treatment with isoproterenol resulted in significant numbers of Apo compared with control [7.9 +/- 2.5 vs. 0.3 +/- 0.3 (SE) cm-2, P < 0.05]. A cohort of animals was subjected to ventricular pacing to induce a tachycardia equivalent to that induced by isoproterenol, and these animals did not show an increase in Apo. The left ventricular hypertrophy induced by 2 wk of abdominal aortic banding also increased Apo ( approximately 7. 2-fold); however, 24 h of isoproterenol infusion did not induce additional Apo in these rats. Thus catecholamines, in the absence of altered systolic load, induce Apo which is not mediated solely by tachycardia. Left ventricular hypertrophy secondary to abdominal aortic banding is associated with Apo, but this does not increase sensitivity to isoproterenol-induced Apo.
为了确定在收缩压负荷无显著增加的情况下，儿茶酚胺本身是否通过凋亡诱导心肌损伤，将大鼠分为两组，分别用赋形剂或异丙肾上腺素（400μg·kg⁻¹·h⁻¹）进行处理。使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法，在石蜡包埋切片中鉴定凋亡心肌细胞（Apo）。结果通过独立的连接酶测定法得到证实。异丙肾上腺素处理组和对照组大鼠的收缩压相当。与对照组相比，用异丙肾上腺素处理24小时后，Apo数量显著增加[7.9±2.5 vs. 0.3±0.3（SE）cm⁻²，P<0.05]。对一组动物进行心室起搏，以诱导与异丙肾上腺素诱导的心动过速相当的心动过速，这些动物的Apo没有增加。腹主动脉缩窄2周诱导的左心室肥厚也增加了Apo（约7.2倍）；然而，在这些大鼠中，输注异丙肾上腺素24小时并未诱导额外的Apo。因此，在收缩压负荷未改变的情况下，儿茶酚胺诱导Apo，这并非仅由心动过速介导。腹主动脉缩窄继发的左心室肥厚与Apo有关，但这并不会增加对异丙肾上腺素诱导的Apo的敏感性。
