Funder J W
Baker Medical Research Instiute, Prahan, Victoria, Australia.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):53-5. doi: 10.1016/0960-0760(95)00021-q.
Mineralocorticoid receptors (MR) have equal affinity for the mineralocorticoid aldosterone, and the physiological glucocorticoids cortisol and corticosterone. In epithelial tissues in vivo, MR are protected against glucocorticoid occupancy by the enzyme 11 beta-hydroxysteroid dehydrogenase, allowing access by the lower circulating levels of the physiological mineralocorticoid aldosterone. In non-epithelial tissues, including the heart and most areas of the central nervous system, MR are not so protected, and their physiological ligand is cortisol/corticosterone. Intracerebroventricular infusion studies have shown that aldosterone occupancy of such unprotected circumventricular MR is necessary for mineralocorticoid hypertension, and the hypertensinogenic effects of peripherally infused aldosterone can be blocked by intracerebroventricular infusion of the MR antagonist RU28318. Prolonged (8 weeks) administration of mineralocorticoids to salt-loaded rats has been shown to be followed by hypertension, cardiac hypertrophy and cardiac fibrosis. Whether the hypertrophy and fibrosis reflect primary effects of aldosterone via cardiac MR, or effects secondary to occupancy of protected, epithelial MR, remains to be determined, as does the mechanism of action of salt loading in this model of mineralocorticoid hypertension.
盐皮质激素受体（MR）对盐皮质激素醛固酮以及生理性糖皮质激素皮质醇和皮质酮具有同等亲和力。在体内的上皮组织中，11β - 羟基类固醇脱氢酶可保护MR免受糖皮质激素占据，从而使循环水平较低的生理性盐皮质激素醛固酮能够与之结合。在包括心脏和中枢神经系统大部分区域在内的非上皮组织中，MR没有这样的保护机制，其生理性配体是皮质醇/皮质酮。脑室内灌注研究表明，此类未受保护的室周MR被醛固酮占据对于盐皮质激素性高血压是必要的，并且脑室内注入MR拮抗剂RU283可以阻断外周注入醛固酮的致高血压作用。给盐负荷大鼠长期（8周）给予盐皮质激素已被证明会导致高血压、心脏肥大和心脏纤维化。肥大和纤维化是反映醛固酮通过心脏MR产生的原发性作用，还是受保护的上皮MR被占据后的继发性作用，仍有待确定，盐负荷在这种盐皮质激素性高血压模型中的作用机制也是如此。
