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目的探讨Losartan拮抗局部肾素-血管紧张系统(RAS)对预防高血压致肾脏靶器官损伤的意义。方法应用细胞培养和Fura-2方法,观察血管紧张素Ⅱ(AugⅡ)和血管紧张素Ⅱ1型受体(AT1受体)拮抗剂Losartan对自发性高血压大鼠(SHR)和正常血压大鼠(WKY)肾小球系膜细胞内游离钙([Ca2+]i)浓度的影响。结果AngⅡ使SHR系膜细胞[Ca2+]i增高,对WKY无影响;AugⅡ对SHR系膜细胞[Ca2+]i的作用可被Losartan抑制并呈剂量依赖关系。结论AngⅡ诱导的肾小球系膜细胞[Ca2+]i增加是经AT1受体介异并被Losartan拮抗。Losartan可能有细胞水平的肾脏保护作用。
Objective To investigate the significance of Losartan antagonism of local renin-angiotensin system (RAS) in preventing renal target organ damage caused by hypertension. Methods Angiotensin Ⅱ (AngⅡ) and Losartan (AT1 receptor) antagonist of angiotensin Ⅱ type 1 receptor (AT1 receptor) were observed in spontaneously hypertensive rats (SHR) and normal blood pressure rats WKY) mesangial cells intracellular free calcium ([Ca2 +] i) concentration. Results AngⅡ increased [Ca2 +] i in SHR mesangial cells and had no effect on WKY. The effect of Aug Ⅱ on [Ca2 +] i in SHR mesangial cells was inhibited by Losartan in a dose-dependent manner. Conclusion AngⅡ-induced increase of [Ca2 +] i in mesangial cells is mediated by AT1 receptor and antagonized by Losartan. Losartan may have a cellular level of renal protection.