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肼屈嗪所致低血压引起的主动脉机械性和生化改变。

Mechanical and biochemical alterations of aorta induced by hydralazine hypotension.

作者信息

Seidel C L, Allen J C, Bowers R L

出版信息

J Pharmacol Exp Ther. 1980 Jun;213(3):514-9.

PMID:7205615
Abstract

Previous experiments from this laboratory indicated that the actomyosin content of aorta from spontaneously hypertensive (SHR) rats was greater than that from normotensive (WKY) rats. The purpose of the present experiments was to determine the effect of hydralazine-induced hypotension on actomyosin content and mechanical properties of aorta from SHR and WKY rats. Ten-week-old WKY and SHR rats were given to tap water or tap water containing 80 mg/l of hydralazine for 2 weeks and at the end of this time the actomyosin content (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), the contractile responses to potassium chloride and phenylephrine and the passive stress-strain properties of the aorta were determined. Hydralazine-treated rats had a significantly lower systolic pressure after 1 week which remained lower for the remainder of the treatment period. Treated WKY and SHR rats exhibited a reduced actomyosin content relative to total protein content of cell number (based on DNA determination). Mechanically, aorta from treated animals showed no change in their passive elastic properties or in their sensitivity (ED50) to either agonist; however, the maximum contractile response to both agonists was significantly reduced. Normalization of force development to actomyosin content indicated: 1) that aorta from SHR rats develop less force for a given amount of actomyosin than WKY aorta; 2) a 2-week period of hydralazine hypotension results in a reduction in force development in both WKY and SHR aorta that can be accounted for by a reduction in cellular actomyosin content; and 3) this period of hydralazine hypotension does not return the contractile effectiveness of actomyosin from SHR aorta to that of actomyosin from WKY aorta.

摘要

本实验室之前的实验表明,自发性高血压(SHR)大鼠主动脉的肌动球蛋白含量高于正常血压(WKY)大鼠。本实验的目的是确定肼屈嗪诱导的低血压对SHR和WKY大鼠主动脉肌动球蛋白含量及力学性能的影响。将10周龄的WKY和SHR大鼠给予自来水或含80 mg/l肼屈嗪的自来水,持续2周,在此时间段结束时,测定肌动球蛋白含量(十二烷基硫酸钠-聚丙烯酰胺凝胶电泳)、对氯化钾和去氧肾上腺素的收缩反应以及主动脉的被动应力-应变特性。肼屈嗪处理的大鼠在1周后收缩压显著降低,在余下的治疗期内一直保持较低水平。与基于DNA测定的细胞数量的总蛋白含量相比,经处理的WKY和SHR大鼠的肌动球蛋白含量降低。在力学方面,经处理动物的主动脉的被动弹性特性或对任何一种激动剂的敏感性(半数有效剂量)均未发生变化;然而,对两种激动剂的最大收缩反应均显著降低。将力的产生归一化至肌动球蛋白含量表明:1)对于给定数量的肌动球蛋白,SHR大鼠主动脉产生的力比WKY大鼠主动脉小;2)2周的肼屈嗪低血压期导致WKY和SHR大鼠主动脉的力产生均降低,这可归因于细胞肌动球蛋白含量的减少;3)这段肼屈嗪低血压期并未使SHR大鼠主动脉肌动球蛋白的收缩效力恢复到WKY大鼠主动脉肌动球蛋白的收缩效力。

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