ARTERIAL SMOOTH-MUSCLE CELL PHENOTYPE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

ARTERIAL SMOOTH-MUSCLE CELL PHENOTYPE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS
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DOI:
10.1161/01.hyp.22.5.665
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发表时间:
1993-11-01
期刊:
影响因子:
8.3
通讯作者:
RAPPAPORT, L
RAPPAPORT, L
中科院分区:
医学1区
文献类型:
--
作者:
CONTARD, F;SABRI, A;RAPPAPORT, L

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这项研究的目的是确定慢性高血压动物动脉中平滑肌细胞的表型,并分析已知的提高动物存活率的治疗方法的效果,但对其高血压状态没有明显影响。易卒中自发性高血压大鼠(SHRSP)饮用1%的钠溶液,从6~13周龄开始,给予吲达帕胺(3 mg/kg/d)或氢氯噻嗪(20 mg/kg/d)两种利尿剂中的一种不治疗或治疗。表型的特征是用针对纤维连接蛋白、α-平滑肌肌动蛋白和非肌肉肌球蛋白的细胞形式(EIIIA)的抗体免疫标记动脉。我们证明了SHRSP的平滑肌细胞表型与Wistar-京都大鼠的不同。表型上的差异是特定于血管类型的:即,非肌肉肌球蛋白在主动脉中的表达增加,而EIIIA纤维连接蛋白和非肌肉肌球蛋白在冠状动脉中的表达增加。这两种利尿剂(1)对血压没有影响,(2)阻止或不阻止中层厚度的增加,(3)防止平滑肌细胞表型和缺血性组织病变的改变。综上所述,上述结果提示,SHRSP患者血管内皮细胞表型的改变与动脉厚度的改变无关。我们认为,维持动脉平滑肌细胞的收缩表型可能是预防严重高血压状态所特有的有害后果的重要参数。
The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analyze the effects of treatments known to increase the survival of the animal without a clear effect on its hypertensive state. Stroke-prone spontaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solution were untreated or treated with one of two diuretics, indapamide (3 mg/kg per day) or hydrochlorothiazide (20 mg/kg per day), from 6 to 13 weeks of age. Phenotype was characterized by the immunolabeling of arteries with antibodies raised against a cellular form (EIIIA) of fibronectin, alpha-smooth muscle actin, and nonmuscle myosin. We demonstrated that phenotypes of smooth muscle cells of the SHRSP differ from those found in Wistar-Kyoto rats. The difference in phenotype is specific for the vessel type: ie, an increased expression of nonmuscle myosin in the aorta and of both EIIIA fibronectin and nonmuscle myosin in the coronary arteries. The two diuretics (1) had no effect on blood pressure, (2) prevented or did not prevent the increase in medial thickness, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that in SHRSP the changes in the phenotype of smooth muscle cells and the thickness of arteries are unrelated events. We propose that the maintenance of the contractile phenotype of the arterial smooth muscle cells could be an essential parameter involved in the prevention of the deleterious consequences characteristic of a severe hypertensive state.