Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Arterioscler Thromb Vasc Biol. 2012 May;32(5):1194-203. doi: 10.1161/ATVBAHA.111.242719. Epub 2012 Mar 1.
The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt.
Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT(1) receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy.
Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone.
盐摄入过多和血浆醛固酮水平升高的合并症对心血管疾病有不良影响。我们评估了与盐摄入相关的醛固酮生物合成反常增加的背后机制。
给予 Dahl 盐敏感型（Dahl-S）和盐抵抗型（Dahl-R）大鼠高盐饮食，通过液相色谱-电喷雾电离-串联质谱法定量测定肾上腺和心脏中的血浆和组织醛固酮水平。在 Dahl-S 大鼠中，我们发现醛固酮生物合成在最初对高盐的适当反应后出现延迟和反常增加。醛固酮生物合成的晚期增加伴随着球状带 CYP11B2 表达的上调以及肾上腺血管紧张素 II 水平和肾素-血管紧张素系统成分的增加。它先于左心室收缩功能障碍和肾功能不全的出现。血管紧张素 AT(1)受体阻断可逆转醛固酮生物合成的反常增加。相比之下，Dahl-R 大鼠维持了最初对醛固酮生物合成的抑制。心脏中的醛固酮水平与血浆和肾上腺中的水平密切平行，双侧肾上腺切除后消失。
Dahl-S 大鼠慢性盐超负荷通过激活肾上腺局部肾素-血管紧张素系统刺激异常的醛固酮产生，从而产生盐摄入过多和血浆醛固酮升高的合并症。
