Savage A O, Dunbar J C, Brown R A
Department of Physiology, Wayne State University School of Medicine, Detroit.
J Cardiovasc Pharmacol. 1995 Aug;26(2):251-8.
The effects of acetaldehyde (ACA) were examined in isolated electrically driven papillary muscle preparations from normal and streptozotocin-treated diabetic rats. Muscles from diabetic rats developed greater tension than those from normal rats. In muscles from both groups, ACA caused concentration-dependent negative inotropic effects that were independent of cholinergic or purinergic mechanisms and were not attributable to nitric oxide (NO) release. ACA was three to five times more potent with regard to its negative inotropic effect in diabetic than in normal rat muscles. A propranolol-sensitive, sympathetically mediated positive inotropic effect occurred at certain concentrations. Decreasing [Ca2+]o from 2.7 to 0.5 mM reduced basal developed force to a significantly greater extent in muscles from normal rats than in those from diabetic rats. In low [Ca2+]o, concentration-response curves to CaCl2 in diabetic muscles were displaced to the left of that in normal muscles, suggesting that diabetic muscles are more sensitive to the positive inotropic effect of added CaCl2 at low [Ca2+]o, whereas at higher [Ca2+]o (> 1 mM), normal muscles developed more force in response to added CaCl2. ACA 10 and 30 mM more readily inhibited CaCl2-induced positive inotropic effect in normal than in diabetic muscles. Force-frequency curves, (negative staircase response) were recorded in both normal and diabetic muscles. In diabetic muscles, the curve exhibited a positive component at the lowest frequencies applied and was displaced to the right of that in normal muscle. ACA concentration-dependently inhibited force development, and diabetic muscles were more susceptible to the negative inotropic effect of ACA, when the stimulation frequency was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
在从正常大鼠和经链脲佐菌素处理的糖尿病大鼠分离得到的电驱动乳头肌制备物中研究了乙醛（ACA）的作用。糖尿病大鼠的肌肉比正常大鼠的肌肉产生更大的张力。在两组肌肉中，ACA均引起浓度依赖性负性肌力作用，该作用独立于胆碱能或嘌呤能机制，且不归因于一氧化氮（NO）释放。就其负性肌力作用而言，ACA在糖尿病大鼠肌肉中的效力是正常大鼠肌肉的三至五倍。在某些浓度下会出现普萘洛尔敏感的、交感神经介导的正性肌力作用。将细胞外钙离子浓度（[Ca2+]o）从2.7 mM降至0.5 mM时，正常大鼠肌肉的基础收缩力降低的程度比糖尿病大鼠肌肉显著更大。在低[Ca2+]o时，糖尿病肌肉对氯化钙的浓度-反应曲线相较于正常肌肉向左移位，这表明在低[Ca2+]o时，糖尿病肌肉对添加氯化钙的正性肌力作用更敏感，而在较高[Ca2+]o（>1 mM）时，正常肌肉对添加氯化钙产生的收缩力更大。10 mM和30 mM的ACA在正常肌肉中比在糖尿病肌肉中更易抑制氯化钙诱导的正性肌力作用。在正常和糖尿病肌肉中均记录了力-频率曲线（负阶梯反应）。在糖尿病肌肉中，该曲线在施加的最低频率时呈现正性成分，且相较于正常肌肉向右移位。当刺激频率增加时，ACA浓度依赖性地抑制力的产生，且糖尿病肌肉对ACA的负性肌力作用更敏感。（摘要截取自250字）
