Ponte A, Sánchez-Ferrer C F, Hernández C, Alonso M J, Marín J
Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universitad Autónoma, Madrid, Spain.
J Hypertens. 1996 Jun;14(6):705-12. doi: 10.1097/00004872-199606000-00005.
To investigate the endothelial modulation of the rat thoracic aorta sodium-potassium ATPase activity and its possible alteration by ageing and hypertension.
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.
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.
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.
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。
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。
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。
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。