Determinants of cardiac fibrosis in experimental hypermineralocorticoid states.
Determinants of cardiac fibrosis in experimental hypermineralocorticoid states.
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DOI：
10.1152/ajpendo.1995.269.4.e657
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发表时间：
1995-10
期刊：
影响因子：
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通讯作者：
M. Young;Geoffrey A. Head;J. Funder
中科院分区：
文献类型：
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作者：
M. Young;Geoffrey A. Head;J. Funder
单肾切除大鼠维持在1.0%NaCl饮用并输注醛固酮（0.75微克/小时）8周，先前已显示发展为高血压、心脏肥大和心脏纤维化。在本研究中，我们已经表明，K+补充（1.0%NaCl加0.4%KCl饮用溶液）既不改变间质也不改变血管周围纤维化对盐皮质激素治疗的反应。第二，大鼠接受0.75微克/小时9 α-氟皮质醇，盐皮质激素和糖皮质激素激动剂，高血压和心脏纤维化的反应，没有心脏肥大。最后，当外周联合输注醛固酮时，脑室内输注盐皮质激素受体拮抗剂RU-28318可以阻止血压升高，但不能阻止心脏肥大或纤维化。我们的结论是，慢性盐皮质激素升高和盐负荷引起的心肌纤维化是一种体液介导的事件，与低钾血症、高血压和心脏肥大无关。仍有待确定的是，在过量盐存在下观察到的纤维化是否代表直接的（例如，心脏）作用或通过对经典上皮醛固酮靶组织的初级作用介导的作用（例如，肾）。
Uninephrectomized rats maintained on 1.0% NaCl to drink and infused with aldosterone (0.75 microgram/h) for 8 wk have previously been shown to develop hypertension, cardiac hypertrophy, and cardiac fibrosis. In the present study we have shown that K+ supplementation (1.0% NaCl plus 0.4% KCl drinking solution) alters neither the interstitial nor the perivascular fibrotic response to mineralocorticoid treatment. Second, rats receiving 0.75 microgram/h 9 alpha-fluorocortisol, a mineralocorticoid and glucocorticoid agonist, respond with hypertension and cardiac fibrosis without cardiac hypertrophy. Finally, intracerebroventricular infusion of the mineralocorticoid receptor antagonist RU-28318 blocks blood pressure elevation, but not cardiac hypertrophy or fibrosis, when aldosterone is coinfused peripherally. We conclude that the myocardial fibrosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally mediated event independent of hypokalemia, hypertension, and cardiac hypertrophy. It remains to be determined whether the fibrosis observed in the presence of excess salt represents a direct (e.g., cardiac) effect of mineralocorticoid hormones or one mediated via a primary action on classical epithelial aldosterone target tissues (e.g., kidney).