Rocha R, Stier C T, Kifor I, Ochoa-Maya M R, Rennke H G, Williams G H, Adler G K
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Endocrinology. 2000 Oct;141(10):3871-8. doi: 10.1210/endo.141.10.7711.
To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and Nomega-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensin II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.
为了确定醛固酮在介导心血管损伤中的作用，我们在心脏损伤大鼠模型中进行了醛固酮切除/替代实验。给饮用1%盐水的雄性大鼠注射血管紧张素II和N-硝基-L-精氨酸甲酯（L-NAME；一氧化氮合成抑制剂）会导致高血压、严重的双心室心肌坏死、蛋白尿以及肾和心脏血管的纤维蛋白样坏死。通过肾上腺切除术或给予选择性醛固酮拮抗剂依普利酮去除醛固酮，可显著减轻心脏和肾脏损伤，而不会显著改变血压。在肾上腺切除、用糖皮质激素替代的L-NAME/血管紧张素II处理的动物中输注醛固酮可恢复损伤。因此，我们确定醛固酮是L-NAME/血管紧张素II诱导的血管损伤的关键介质，其机制显然独立于其对收缩压的影响。
