压力超负荷性心肌肥厚发病机制的研究

目的:探讨α1、β受体阻断剂派唑嗪(Prazosin,Pra)、心得安(Propra-nolol,Pro)及钙离子拮抗剂尼群地平(Nitrendipine,Nit)在压力超负荷性心肌肥厚发病学中的意义。方法:采用Pra、Pro和Nit治疗大鼠腹主动脉缩窄所致左室肥厚(LVH)。结果:Pra和Nit能抑制早期肥厚心肌c-fosmRNA表达,6周后Pra组和Nit组较LVH组之BP,LVW/BW均显著下降,同时心脏舒张功能改善,Na+-K+ATPase活性增强;而Pro不能有效改善LVH。结论:Pra和Nit治疗成功预防了心肌肥厚的发生,而Pro不能。提示儿茶酚胺参与压力超负荷性心肌肥厚的形成,其效应不仅涉及后负荷的高低,也可通过α1肾上腺素能受体而不是β肾上腺素能受体对心肌产生直接性致肥大作用,同时钙离子可作为第二信使参与引起心肌细胞肥大的信息传递。

Study of Mechanism of Pressure Overload-Induced Myocardial Hypertrophy in Rats

Objective: To study the roles of Pra (Prazosin), Pro (Propranolol) and Nit (Nitrendipine) in pressure overload-induced myocardial hypertrophy in rats.Method: Rats with left ventricular hypertrophy (LVH) induced by abdominal aorta constriction were treated with Pra, Pro and Nit respectively.Results: Pra and Nit inhibit increasing of c-fos mRNA level in the early stage of pressure overload-induced myocardial hypertrophy. 6 weeks after operation, in the Pra group and the Nit group, blood pressure, left ventricular weight/body weight (LVW/BW) significantly decreased, while the diastolic function of the left ventricle improved and the activity of Na~+-K~+ ATPase markedly increased.Pro can't inhibit the development of LVH effectively.Conclusion: Pra and Nit but not Pro can successfully prevent the development of LVH. It's implicated that catecholamine is involved in the development of pressure overload-induced myocardial hypertrophy. And catecholamine can not only affect the afterload, but also have the direct effect on myocardial hypertrophy through α_1-adrenergic receptors but not β-adrenergic receptors. In addition, Ca~(2+) as a second messenger is involved in the signal transduction that caused pressure overload-induced myocardial hypertrophy.