von Lutterotti N, Camargo M J, Campbell W G, Mueller F B, Timmermans P B, Sealey J E, Laragh J H
Department of Medicine, Cornell University Medical College, New York, NY 10021.
J Hypertens. 1992 Sep;10(9):949-57.
To study the effects of blockade of the renin-angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan.
DSS rats (n = 186) were fed 8% NaCl from 6 to 16 weeks of age. One group received losartan whilst the control group was untreated. Changes in blood pressure and plasma renin activity (PRA), as well as renal and cerebrovascular damage and survival were assessed during the study.
Losartan blunted the blood pressure rise only transiently. Salt loading suppressed PRA in both groups until week 4 and thereafter it rose more markedly in the treated group. With no treatment renal lesions were first detected at 2 weeks, and strokes at 6 weeks. However, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival. PRA correlated with renal damage and the incidence of strokes in both groups. Blood pressure only partially affected survival, but did not correlate with stroke incidence.
These results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure.
使用血管紧张素II受体拮抗剂氯沙坦，研究阻断肾素-血管紧张素系统对Dahl盐敏感（DSS）大鼠高血压发展、靶器官损害及死亡率的影响。
186只DSS大鼠在6至16周龄时喂食8%氯化钠。一组给予氯沙坦，对照组不做处理。研究期间评估血压和血浆肾素活性（PRA）的变化，以及肾和脑血管损害及生存率。
氯沙坦仅短暂抑制血压升高。两组在第4周前盐负荷均抑制PRA，此后治疗组PRA升高更明显。未治疗时，2周时首次检测到肾损害，6周时出现中风。然而，氯沙坦可短暂降低肾损害和脑血管病变（中风）的发生率并延缓其进展，还可提高生存率。两组中PRA均与肾损害及中风发生率相关。血压仅部分影响生存率，但与中风发生率无关。
这些结果表明，虽然血压升高依赖于钠负荷，但盐负荷的DSS大鼠的发病率和死亡率与肾素-血管紧张素系统的激活有关，且仅部分与血压相关。
