粉防己碱对心脏与血管重塑的影响

粉防己碱早年即已作为降压药应用,膜片箝及钙受体研究认为属特殊结构的钙拮抗剂.高血压患者80％伴左心室肥厚,此类患者发生心血管事件较高血压不伴心肌肥厚者高出8-10倍.本研究利用三种模型高血压(SHR,RHR,高肾素型;DOCA- salt HR 低肾素型)形成心肌血管重塑,研究了粉防己碱的防治疗效.粉防己碱灌胃9周后,明显减轻心脏(左室重/体重)血管(中膜厚度,壁/腔比值,血管横截面)重量及胶原含量,明显改善心脏血流动力学,特别改善心舒张功能,降低钙通道的受体密度,减少钙过负荷,增加心肌myosin等ATP酶活性,改善血管异常反应性,抑制血管增殖,诱导和敏化高血压大鼠血管平滑肌细胞凋亡,保护血管内皮功能,增加 NO产生.上述作用都促使心脏血管重塑得以逆转.因此是一个值得开发的既降压又防治心血管重塑的优秀药物.

Effects of tetrandrine on cardiac and vascular remodeling

Tetrandrine (Tet) is an alkaloid isolated from the Chinese herb Radix of Stephaniae tetrandrae S Moore. Cardiac and vascular remodeling confers a very definite risk of increased cardiovascular morbidity and mortality. Remodeling reversal has been achieved in human and experimental animals treated with some antihypertensive drugs but not all. This review will focus on cardiovascular remodeling and therapeutic effects of Tet. Three models, SHR, RHR (high renin), and DOCA-Salt HR (low renin) were used. Left ventricular and vascular remodeling had been developed in rats with 8-week untreated hypertension. Tet was administrated by ig 50 mg/kg/d for 9 weeks. Tet lowered SBP, left ventricular weight to body weight ratio, vascular media thickness, media to lumen ratio, cardiac and vascular wet weight, and collagen content. Tet decreased markedly the density and total number of dihydropyridine binding sites and also decreased Ca2+ overload in myocardium and vessels. Tet improved haemodynamic changes during remodeling special diastolic function such as LV compliance and stiffness, increased cardiac myosin ATPase activity and Na+-K+, Ca2+ ATPase activity, and normalized vascular reactivity. Tet inhibited proliferation of vascular smooth muscle cells, induced and sensitized VSMCs to pro-apoptosis stimulation, improved the endothelial function, and increased NO production. These results suggest that Tet was not only an anti-hypertensive drug but also an excellent drug to reverse cardiac and vascular remodeling.