Young M, Head G, Funder J
Baker Medical Research Institute, Prahran, Victoria, Australia.
Am J Physiol. 1995 Oct;269(4 Pt 1):E657-62. doi: 10.1152/ajpendo.1995.269.4.E657.
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).
之前的研究表明，饮用1.0%氯化钠溶液并连续8周输注醛固酮（0.75微克/小时）的单侧肾切除大鼠会出现高血压、心脏肥大和心脏纤维化。在本研究中，我们发现补充钾（1.0%氯化钠加0.4%氯化钾饮用溶液）既不会改变间质纤维化，也不会改变血管周围对盐皮质激素治疗的纤维化反应。其次，接受0.75微克/小时9α-氟皮质醇（一种盐皮质激素和糖皮质激素激动剂）的大鼠会出现高血压和心脏纤维化，但无心脏肥大。最后，当外周共同输注醛固酮时，脑室内输注盐皮质激素受体拮抗剂RU-28318可阻断血压升高，但不能阻断心脏肥大或纤维化。我们得出结论，慢性盐皮质激素升高和盐负荷导致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。在盐过量情况下观察到的纤维化是盐皮质激素的直接（如对心脏）作用，还是通过对经典上皮醛固酮靶组织（如肾脏）的主要作用介导，仍有待确定。
