早期应用Losartan对高血压蛋白尿的影响

对探讨高血压病微量蛋白尿的形成机制及早期应用Losartan对其的保护作用。观察不同月龄（3月龄和8月龄）高血压鼠的血压，尿蛋白和肾功能以及血管内皮和肾小球结构的不同改变。与同龄正常组相比较，3月龄高血压鼠电镜下已有血管内皮损害，肾小球基底膜亦见轻度增厚，尿蛋白增多，且与血压及血管内皮病变呈正相关；8月龄高血压鼠无论血管内皮和肾小球均损害严重，除基底膜增厚和系膜区扩张外还有系膜细胞增生肥大，血肌酐无明显变化，尿蛋白增高与血管内皮和肾小球病变密切相关。经Losartan治疗后不但尿蛋白明显减少。而且血管内皮和系膜细胞的过度增生肥大被有效地抑制。系膜区体密度及细胞外基质明显减小，基底膜得到修复，提示高血压蛋白尿的出现与靶器官损害密切相关，早期应用Losartan能改善肾循环，保护血管，肾脏，阻止后期的肾小球硬化。

Effects of Early Intervention with Losartan for Hypertensive Microalbuminuria

Aim To investigate the mechanisms of hypertensive microalbuminuria and the benefit of early intervention with losartan. Methods The investigation comprised normotensive control (WKY) and hypertensive group (SHR) of rats, of which blood pressure, microalbuminuria, renal function and relevant ultrastructural indexes in vessel and glomerulus with transmission electronic microscope were acquired at three month old and eight month old. Results In three month old SHR, electronic microscopic observation demonstrated early impairment of vessel endothelium and slight lesion of glomerular basement membrane compared with age matched controls. As a result, microalbuminuria that correlated with blood pressure and impairment of endothelium has been shown. At eight month old, creatinine level has not elevated in spite of the aggravation of impairment of vessel endothelium and lesion of glomerulus, which was associated with microalbuminuria. However, microalbuminuria was unrelated to blood pressure at this stage. With the treatment of losartan, not only reduction of microalbuminuria was achieved but also decrease in volume density of vessel endothelium, mesangial cells and mesangial area was shown. Conclusions The mechanism led to microalbuminuria in hypertension may vary according to the severity of the hypertensive condition. Early intervention with losartan can inhibit glomerulosclerosis more than lower blood pressure.