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衰老和高血压对大鼠主动脉哇巴因诱导的收缩及钠泵活性的内皮调节作用

Effect of ageing and hypertension on endothelial modulation of ouabain-induced contraction and sodium pump activity in the rat aorta.

作者信息

Ponte A, Sánchez-Ferrer C F, Hernández C, Alonso M J, Marín J

机构信息

Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universitad Autónoma, Madrid, Spain.

出版信息

J Hypertens. 1996 Jun;14(6):705-12. doi: 10.1097/00004872-199606000-00005.

Abstract

OBJECTIVE

To investigate the endothelial modulation of the rat thoracic aorta sodium-potassium ATPase activity and its possible alteration by ageing and hypertension.

METHODS

Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) aged 5 weeks, 3, 6, 12 and 18 months were anaesthetized. Their aortae were dissected and divided into cylindrical segments and vasomotor responses obtained in segments with or without endothelium were recorded on a polygraph.

RESULTS

Endothelium removal increased ouabain responses in young (aged 3 and 6 months) WKY rat aortic segments, but reduced those obtained in old (aged 18 months) WKY rat segments and in segments from SHR aged 3, 6 and 12 months. An enhancement of contractions in response to ouabain with age was observed in both strains, but it occurred at earlier ages in vessels from SHR. At ages 3 and 6 months, responses to ouabain were higher in intact vessels from SHR than they were in those from WKY, but were lower in endothelium-denuded vessels. In aortic segments from 6-month-old WKY rats and SHR, ouabain reduced or abolished potassium-induced relaxations in segments with or without endothelium, respectively. In vessels from SHR and WKY rats aged 18 months, ouabain abolished potassium-induced relaxations both in intact and in endothelium-denuded vessels.

CONCLUSIONS

Endothelium of WKY rat aorta might release a factor in response to ouabain that modulates its contraction negatively. Endothelium of SHR and old WKY rat aorta releases a contracting factor that modulates ouabain contractions positively. Thus, the inhibitory effect of endothelium on contractions induced by ouabain might be lost as a consequence both of hypertension and of age, being replaced by an endothelium-dependent contracting factor that facilitates ouabain responses.

摘要

目的

研究大鼠胸主动脉钠钾ATP酶活性的内皮调节作用,以及衰老和高血压对其可能产生的改变。

方法

对5周龄、3、6、12和18月龄的雄性自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY)进行麻醉。解剖其主动脉,切成圆柱形节段,在有或无内皮的节段上记录血管舒缩反应,并通过多导记录仪进行记录。

结果

去除内皮后,年轻(3和6月龄)WKY大鼠主动脉节段对哇巴因的反应增强,但老年(18月龄)WKY大鼠节段以及3、6和12月龄SHR的节段对哇巴因的反应减弱。在两种品系中均观察到,随着年龄增长,对哇巴因的收缩反应增强,但SHR血管的这种增强在更早的年龄出现。在3和6月龄时,SHR完整血管对哇巴因的反应高于WKY,但在内皮剥脱血管中则较低。在6月龄WKY大鼠和SHR的主动脉节段中,哇巴因分别降低或消除了有或无内皮节段中钾诱导的舒张。在18月龄SHR和WKY大鼠的血管中,哇巴因在完整和内皮剥脱血管中均消除了钾诱导的舒张。

结论

WKY大鼠主动脉内皮可能会释放一种因子来响应哇巴因,从而对其收缩产生负向调节作用。SHR和老年WKY大鼠主动脉内皮释放一种收缩因子,对哇巴因收缩产生正向调节作用。因此,内皮对哇巴因诱导收缩的抑制作用可能会因高血压和衰老而丧失,取而代之的是一种促进哇巴因反应的内皮依赖性收缩因子。

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