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糖尿病大鼠心脏对钙的机械反应受损:硝苯地平治疗可逆转

Impaired mechanical response to calcium of diabetic rat hearts: reversal by nifedipine treatment.

作者信息

Shimabukuro M, Shinzato T, Higa S, Nagamine F, Murakami K, Takasu N

机构信息

Second Department of Internal Medicine, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa.

出版信息

J Cardiovasc Pharmacol. 1995 Sep;26(3):495-502. doi: 10.1097/00005344-199509000-00022.

Abstract

Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca2+ was studied using isolated working hearts. At 14 weeks of age, 7 weeks after a streptozotocin injection, diabetic rats had a lower body weight and heart weight than controls, and an increase in heart weight-to-body weight ratio. Nifedipine treatment did not alter these parameters of controls, but decreased the heart weight and heart weight-to-body weight ratio of diabetic rats without affecting the body weight. In diabetic rats, systolic blood pressure was decreased compared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and reduced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In control rats, LV developed pressure, LV +/- dP/dt, and cardiac work were unchanged regardless of the increment in preload at 1.25, 1.88, and 2.50 mM Ca2+. However, the responses of diabetic rats were decreased with an increment in preload at 2.5 mM Ca2+. Nifedipine treatment produced a partial recovery of all four parameters at 2.5 mM Ca2+ in diabetic rats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca2+ concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca2+ conditions.

摘要

用含0.03%硝苯地平的饲料对链脲佐菌素诱导的糖尿病大鼠和年龄匹配的对照大鼠进行6周治疗,并使用离体工作心脏研究对Ca2+的机械反应。在14周龄时,即链脲佐菌素注射7周后,糖尿病大鼠的体重和心脏重量低于对照组,心脏重量与体重之比增加。硝苯地平治疗未改变对照组的这些参数,但降低了糖尿病大鼠的心脏重量和心脏重量与体重之比,而不影响体重。与对照组相比,糖尿病大鼠的收缩压降低(124±5 vs. 137±6 mmHg,p<0.01),硝苯地平治疗使其进一步降低(111±4 mmHg,p<0.01)。在对照大鼠中,无论在1.25、1.88和2.50 mM Ca2+时预负荷增加多少,左心室舒张末压、左心室±dP/dt和心脏作功均无变化。然而,在2.5 mM Ca2+时,随着预负荷增加,糖尿病大鼠的反应降低。硝苯地平治疗使糖尿病大鼠在2.5 mM Ca2+时这四个参数均部分恢复。在所有Ca2+浓度下,对照组和糖尿病大鼠心脏的心肌Ca2+含量和肌膜脂质过氧化相似,硝苯地平治疗不影响这些值。结果表明,慢性硝苯地平治疗可改善高Ca2+条件下糖尿病大鼠心脏的收缩性。

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