Costello-Boerrigter Lisa C, Boerrigter Guido, Harty Gail J, Cataliotti Alessandro, Redfield Margaret M, Burnett John C
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA.
Hypertension. 2007 Sep;50(3):481-8. doi: 10.1161/HYPERTENSIONAHA.107.088534. Epub 2007 Jul 16.
Unlike healthy subjects, overt congestive heart failure cannot "escape" the sodium- and water-retaining actions of mineralocorticoid excess. It is undefined whether escape occurs in asymptomatic left ventricular dysfunction (ALVD), which is characterized by preserved sodium homeostasis, natriuretic peptide activation, and normal circulating aldosterone. We hypothesized that, in ALVD, mineralocorticoid excess with exogenous deoxycorticosterone acetate (DOCA) would overwhelm renal compensatory mechanisms, resulting in sodium and water retention, and promote renal and cardiac collagen deposition. ALVD was induced in 2 groups (N=5 each) of dogs by tachypacing at 180 bpm. Urine was collected daily and blood drawn at baseline and days 2, 5, 8, and 11. One group served as control (ALVD), and the other received DOCA (ALVD+DOCA) starting at day 2 of pacing. Urine flow and sodium excretion were unchanged in the ALVD group. In ALVD+DOCA, urine flow and sodium excretion decreased on the first 2 days DOCA was given but normalized starting day 4. Urine flow and urinary cGMP excretion increased in ALVD+DOCA after DOCA escape. Plasma atrial natriuretic peptide, B-type natriuretic peptide, and cGMP increased equally in both groups. There were no differences in cardiorenal and hemodynamic parameters in an acute study on day 11. Although renal collagen area fraction was similar, left ventricular collagen area fraction in ALVD+DOCA was significantly higher than in ALVD (3.3+/-0.4% versus 2.0+/-0.2%; P=0.012). We conclude that ALVD can escape the sodium- and water-retaining effects of mineralocorticoid excess. Despite renal escape, increased left ventricular collagen deposition suggests that the heart but not the kidney failed to escape the tissue effects of DOCA.
与健康受试者不同，明显的充血性心力衰竭无法“逃脱”盐皮质激素过多所致的钠水潴留作用。目前尚不清楚在以钠稳态维持、利钠肽激活和循环醛固酮正常为特征的无症状左心室功能障碍（ALVD）中是否会发生逃脱现象。我们推测，在ALVD中，外源性醋酸脱氧皮质酮（DOCA）导致的盐皮质激素过多会压倒肾脏的代偿机制，导致钠水潴留，并促进肾脏和心脏胶原沉积。通过以180次/分钟的频率快速起搏，在两组（每组N = 5只）犬中诱导出ALVD。每天收集尿液，并在基线以及起搏第2、5、8和11天采集血液样本。一组作为对照（ALVD），另一组从起搏第2天开始接受DOCA（ALVD + DOCA）。ALVD组的尿流量和钠排泄量未发生变化。在ALVD + DOCA组中，给予DOCA的头2天尿流量和钠排泄量下降，但从第4天开始恢复正常。DOCA逃脱后，ALVD + DOCA组的尿流量和尿cGMP排泄量增加。两组的血浆心房利钠肽、B型利钠肽和cGMP均等量增加。在第11天的急性研究中，心脏肾脏和血流动力学参数没有差异。尽管肾脏胶原面积分数相似，但ALVD + DOCA组的左心室胶原面积分数显著高于ALVD组（3.3±0.4%对2.0±0.2%；P = 0.012）。我们得出结论，ALVD可以逃脱盐皮质激素过多所致的钠水潴留效应。尽管肾脏出现逃脱现象，但左心室胶原沉积增加表明心脏而非肾脏未能逃脱DOCA的组织效应。
