年龄和乙酰甲胆碱对糖尿病大鼠离体心脏心率和冠脉血流量的影响。

Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

作者信息

Li X S, Tanz R D, Chang K S

机构信息

Department of Pharmacology, Oregon Health Sciences University, School of Medicine, Portland 97201.

出版信息

Br J Pharmacol. 1989 Aug;97(4):1209-17. doi: 10.1111/j.1476-5381.1989.tb12580.x.

DOI:10.1111/j.1476-5381.1989.tb12580.x

PMID:2477102

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854615/

Abstract

Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

摘要

采用Langendorff方法灌注来自6周、12周和24周链脲佐菌素（STZ）诱导的糖尿病大鼠的离体心脏，在平衡60分钟后出现显著心动过缓。与年龄匹配的对照组（268±15；P＜0.001）以及胰岛素治疗的糖尿病大鼠（232±17；P＜0.01）相比，12周糖尿病大鼠心脏的心率显示出最大程度的心动过缓，但到52周时，三组的心率相似。随着年龄增长，STZ糖尿病对大鼠离体灌注心脏心率的影响保持不变，但对照组和糖尿病+胰岛素组的心率下降。2. 发现来自6至52周STZ处理大鼠的心脏对乙酰甲胆碱的负性变时作用更敏感，12周龄动物的心脏差异最为显著。阿托品（10⁻⁷ M）不影响年龄匹配的对照组或糖尿病大鼠的静息心率，但能阻断两者中乙酰甲胆碱（2.6×10⁻⁶ M）诱导的心动过缓，这表明糖尿病性心动过缓的作用部位不是毒蕈碱受体。3. 在平衡期末，12周糖尿病动物心脏的冠脉流量显著减少。在自发搏动的糖尿病大鼠心脏中，给予乙酰甲胆碱（2.6×10⁻⁶ M）后，12周、24周和52周糖尿病心脏的冠脉流量下降更为显著。然而，当进行电起搏（5 Hz）时，除了52周时年龄匹配的对照组和糖尿病组之间，三组对乙酰甲胆碱的反应没有差异。这表明乙酰甲胆碱对糖尿病心脏冠脉流量的更明显降低是其负性变时作用的继发效应。4. 一般来说，胰岛素治疗的糖尿病动物心脏在有或没有乙酰甲胆碱的情况下，其反应与年龄匹配的对照组相似。