Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Hypertension. 2012 Jul;60(1):98-105. doi: 10.1161/HYPERTENSIONAHA.112.191767. Epub 2012 May 29.
Dietary salt intake is a major determinant of the activation state of renin-angiotensin-aldosterone system. Given the important role of the renin-angiotensin-aldosterone system in plaque accumulation, we investigated its role in the development of atherogenesis associated with sodium intake in apolipoprotein E knockout mice. Six-weeks of a low-salt diet (containing 0.03% sodium) resulted in a 4-fold increase in plaque accumulation in apolipoprotein E knockout mice when compared with mice receiving normal chow (containing 0.30% sodium). This was associated with activation of the renin-angiotensin-aldosterone system, increased vascular expression of adhesion molecules and inflammatory cytokines, and increased adhesion of labeled leukocytes across the whole aorta on a dynamic flow assay. These changes were blocked with the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg per day). A high-salt diet (containing 3% sodium) attenuated vascular inflammation and atherogenesis, associated with suppression of the renin-angiotensin-aldosterone system, although systolic blood pressure levels were modestly increased (5 ± 1 mmHg). Constitutive activation of the renin-angiotensin-aldosterone system in angiotensin-converting enzyme 2 apolipoprotein E knockout mice was also associated with increased atherosclerosis and vascular adhesion, and this was attenuated by a high-salt diet associated with suppression of the renin-angiotensin-aldosterone system. By contrast, a low-salt diet failed to further activate the renin-angiotensin-aldosterone system or to increase atherosclerosis in angiotensin-converting enzyme 2 apolipoprotein E knockout mice. Together, these data validate a relationship between salt-mediated renin-angiotensin-aldosterone system activation and atherogenesis, which may partly explain the inconclusive or paradoxical findings of recent observational studies, despite clear effects on blood pressure.
饮食盐摄入量是肾素-血管紧张素-醛固酮系统激活状态的主要决定因素。鉴于肾素-血管紧张素-醛固酮系统在斑块积聚中的重要作用，我们研究了它在载脂蛋白 E 基因敲除小鼠钠摄入相关动脉粥样硬化形成中的作用。与接受普通饲料（含 0.30%钠）的小鼠相比，低钠饮食（含 0.03%钠） 6 周可使载脂蛋白 E 基因敲除小鼠的斑块积聚增加 4 倍。这与肾素-血管紧张素-醛固酮系统的激活、血管黏附分子和炎症细胞因子表达增加以及在动态流动测定中整个主动脉上标记白细胞的黏附增加有关。这些变化可被血管紧张素转换酶抑制剂培哚普利（2mg/kg/天）阻断。高盐饮食（含 3%钠）可减轻血管炎症和动脉粥样硬化形成，与肾素-血管紧张素-醛固酮系统的抑制有关，尽管收缩压水平略有升高（5±1mmHg）。血管紧张素转换酶 2 载脂蛋白 E 基因敲除小鼠中肾素-血管紧张素-醛固酮系统的组成性激活也与动脉粥样硬化和血管黏附增加有关，而高盐饮食可抑制肾素-血管紧张素-醛固酮系统，从而减轻这种情况。相比之下，低钠饮食未能进一步激活肾素-血管紧张素-醛固酮系统或增加血管紧张素转换酶 2 载脂蛋白 E 基因敲除小鼠的动脉粥样硬化。总之，这些数据验证了盐介导的肾素-血管紧张素-醛固酮系统激活与动脉粥样硬化之间的关系，这可能部分解释了最近观察性研究结果的不一致或矛盾，尽管对血压有明确影响。
