Kornel L, Rafelson M E, Hayashi T, Kanamarlapudi N, Anderson K M
Rush-Presbyterian-St. Luke's Medical Center, Department of Medicine, Chicago, Ill.
Clin Physiol Biochem. 1988;6(3-4):188-200.
The role of arterial receptors to mineralocorticoids (MC) and glucocorticoids (GC) in the induction by MC and GC of changes in transmembrane transport of sodium (Na+) and water was investigated. Implantation of Silastic rubber strips impregnated with 11-desoxycorticosterone acetate (DOCA) in rabbits was followed by a marked increase in vascular smooth muscle cell membrane permeability to Na+ and hypertension. Both of these effects were preventable with progesterone, an anti-MC at the steroid-receptor level, implanted in relative excess simultaneously with DOCA, in approximately 50% of the implanted animals. The other 50% were hydroxylating in vivo progesterone to 11-desoxycorticosterone (DOC) efficiently enough not to yield the necessary ratio of progesterone to DOC for the sufficient MC receptor blockage. In vascular smooth muscle cell culture, grown in the presence of steroids, GC but not MC increased intracellular water space. This increase was preventable by a potent synthetic anti-GC,RU 38486, a steroid with high affinity for GC receptors, added to culture medium along with GC. These results provide evidence that both the in vivo effect of MC on Na+ permeability and the induction of hypertension, and the in vitro effect of GC on water transport in cultured vascular smooth muscle cells are elicited through the receptor-mediated molecular mechanism(s) for action of these steroids in the arterial wall.
研究了动脉受体对盐皮质激素(MC)和糖皮质激素(GC)的反应,以及MC和GC诱导钠(Na +)和水跨膜转运变化的作用。给兔子植入浸有醋酸11-脱氧皮质酮(DOCA)的硅橡胶条后,血管平滑肌细胞膜对Na +的通透性显著增加,并出现高血压。在大约50%的植入动物中,同时植入相对过量的孕酮(一种在类固醇受体水平上的抗MC),可预防这两种效应。另外50%的动物在体内将孕酮有效地羟基化为11-脱氧皮质酮(DOC),以至于无法产生足够比例的孕酮与DOC来充分阻断MC受体。在类固醇存在下培养的血管平滑肌细胞中,GC而非MC增加了细胞内水空间。这种增加可通过一种强效合成抗GC药物RU 38486(一种对GC受体具有高亲和力的类固醇)与GC一起添加到培养基中加以预防。这些结果表明,MC对Na +通透性的体内效应和高血压的诱导,以及GC对培养的血管平滑肌细胞中水转运的体外效应,都是通过这些类固醇在动脉壁中作用的受体介导分子机制引发的。