Arterial receptors for adrenal steroids and transport of electrolytes in vascular smooth muscle.
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.
Kornel
L
L
Rush-Presbyterian-St. Luke's Medical Center, Department of Medicine, Chicago, Ill.
Rafelson
M E
ME
Hayashi
T
T
Kanamarlapudi
N
N
Anderson
K M
KM
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003900:Desoxycorticosterone / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D015735:Mifepristone; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D004963:Estrenes; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D014867:Water; D015735:Mifepristone; D003900:Desoxycorticosterone; D011374:Progesterone; D012964:Sodium