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年轻自发性高血压大鼠微血管内血小板血栓形成

Platelet thrombus formation in microvessels of young spontaneously hypertensive rats.

作者信息

Lominadze D, Joshua I G, Catalfamo J L, Schuschke D A

机构信息

Center for Applied Microcirculatory Research, University of Louisville, KY 40292, USA.

出版信息

Clin Exp Hypertens. 1998 Nov;20(8):917-37. doi: 10.3109/10641969809053255.

Abstract

We have previously shown an increase in platelet-to-endothelial cell adhesion in microvessels of spontaneously hypertensive rats (SHR) during the established stage of hypertension (12 weeks). The objective of the current study was to determine if the platelet-to-endothelial cell interaction would be altered in the early developmental phase of hypertension. Male weanling (3 weeks old) SHRs (n=6) and age matched normotensive Wistar-Kyoto (WKY) rats (n=6) were used to study platelet thrombus formation. Intravascular fluorescein isothiocyanate tagged to bovine serum albumin was activated with 450-490 nm light to induce thrombus formation in microvessels. Plasma concentrations of von Willebrand factor (vWF), fibrinogen and fibronectin (FN) were measured in rats during both early (3 week) and established stages of hypertension development. Thrombus initiation time in both arterioles (847+/-85 sec) and venules (222+/-40 sec) of young SHRs was significantly shorter (p<0.05) than in arterioles (1270+/-88 sec) and venules (630+/-72 sec) of age matched WKY rats respectively. After thrombus appearance, however, overall time for vessel occlusion in arterioles (2590+/-90 sec) and venules (935+/-131 sec) of SHRs was not different compared to that in arterioles (2650+/-191 sec) and venules (1240+/-93 sec) of age matched WKY rats. The plasma concentration of FN was increased (p<0.05) in both the young (0.9+/-0.1 mg/ml) and mature (1.1+/-0.2 mg/ml) hypertensive rats (n=5) compared to that in young (0.6+/-0.03 mg/ml) and mature (0.5+/-0.1 mg/ml) WKY rats (n=5), while fibrinogen content (3.6 +/-0.3 mg/ml) was elevated (p<0.05) only in mature SHRs (n=5) compared to that (2.7+/-0.02 mg/ml) in age matched WKY rats (n=5). The plasma concentration of vWF was similar to that of controls in either age group of hypertensive animals. These results suggest that changes in platelet-to-endothelial cell interactions occur in the early phase of genetic hypertension development in rats, and appears to result from alteration of plasma concentration of adhesion proteins.

摘要

我们之前已经表明,在高血压确立阶段(12周),自发性高血压大鼠(SHR)微血管中血小板与内皮细胞的黏附增加。本研究的目的是确定在高血压早期发育阶段血小板与内皮细胞的相互作用是否会发生改变。使用雄性断奶(3周龄)SHR(n = 6)和年龄匹配的正常血压Wistar-Kyoto(WKY)大鼠(n = 6)来研究血小板血栓形成。用450 - 490nm光激活与牛血清白蛋白结合的血管内异硫氰酸荧光素,以诱导微血管中的血栓形成。在高血压发展的早期(3周)和确立阶段,测量大鼠血浆中血管性血友病因子(vWF)、纤维蛋白原和纤连蛋白(FN)的浓度。年轻SHR的小动脉(847±85秒)和小静脉(222±40秒)中的血栓起始时间分别显著短于(p < 0.05)年龄匹配的WKY大鼠小动脉(1270±88秒)和小静脉(630±72秒)中的血栓起始时间。然而,血栓出现后,SHR小动脉(2590±90秒)和小静脉(935±131秒)的血管阻塞总时间与年龄匹配的WKY大鼠小动脉(2650±191秒)和小静脉(1240±93秒)的血管阻塞总时间相比并无差异。与年轻(0.6±0.03mg/ml)和成熟(0.5±0.1mg/ml)的WKY大鼠(n = 5)相比,年轻(0.9±0.1mg/ml)和成熟(1.1±0.2mg/ml)的高血压大鼠(n = 5)血浆中FN浓度均升高(p < 0.05),而仅成熟SHR(n = 5)的纤维蛋白原含量(3.6±0.3mg/ml)高于年龄匹配的WKY大鼠(n = 5)(2.7±0.02mg/ml)(p < 0.05)。高血压动物任一年龄组的血浆vWF浓度与对照组相似。这些结果表明,血小板与内皮细胞相互作用的变化发生在大鼠遗传性高血压发展的早期阶段,并且似乎是由黏附蛋白血浆浓度的改变引起的。

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