Differential regulation of na, k-atpase gene expression by gluco-
and mineralocorticoids in vascular smooth muscle cells.
Muto, S., J. Nemoto, A. Ohtaka, Y. Watanabe, M. Yamaki, K. Kawakami,
K. Nagano, and Y. Asano.
Departments of Nephrology and Biology, Jichi Medical School,
Minamikawachi. Tochigi 329-04, Japan
APStracts 2:0333C, 1995.
To determine whether gluco- and mineralocorticoids have specific
actions on Na, K-ATPase gene expression in vascular tissue, we used
Northern blot analysis to compare the effects of dexamethasone and
aldosterone on Na,K-ATPase [alpha]1 and [beta]1 subunit mRNA
expression in cultured vascular smooth muscle cells from rat aortae.
Dexamethasone (DEX) at 10-6 M increased [alpha]1 mRNA level 2.5-fold
at 24 hrs and [beta]1 mRNA level 9.9-fold at 12 hrs. Aldosterone
(ALDO) at 10-6 M increased [alpha]1 mRNA level 2.7-fold at 48 hrs and
[beta]1 mRNA level 10.9-fold at 6hrs. The half maximal stimulation of
both [alpha]1 and [beta]1 mRNA levels occurred at a concentration of
5-7 x 10-9 M DEX, whereas it occurred at a concentration of 2-3 x 10
-9 M ALDO. The glucocorticoid receptor antagonist RU 38486 inhibited
both DEX- and ALDO-mediated induction of [beta]1 mRNA. The
mineralocorticoid receptor antagonist spironolactone inhibited ALDO
-mediated induction of [beta]1 mRNA, whereas it had no effect on DEX
-mediated induction of [beta]1 mRNA. Removal of Na from the
extracellular medium (isosmotic replacement with choline) caused no
effect on DEX-mediated induction of [beta]1 mRNA, whereas it
inhibited ALDO-mediated induction of [beta]1 mRNA. Addition of a
specific inhibitor of the Na/H exchange, ethylisopropylamiloride, had
no effect on DEX-mediated induction of [beta]1 mRNA, whereas it
resulted in a significant inhibition of ALDO-mediated induction of
[beta]1 mRNA. We conclude: (a) both DEX and ALDO induce Na, K-ATPase
[alpha]1 and [beta]1 mRNA expression in a time- and dose-dependent
manner; (b) DEX-mediated induction of [beta]1 mRNA occurs only
through glucocorticoid receptors, whereas ALDO-mediated induction of
[beta]1 mRNA occurs through both gluco- and mineralocorticoid
receptors; and (c) DEX-mediated induction of [beta]1 mRNA occurs
through Na-independent mechanisms, whereas ALDO-mediated induction of
[beta]1 mRNA, at least in part, occurs through Na-dependent
mechanisms, including stimulation of the Na/H exchange.
Received 21 April 1995; accepted in final form 5 September 1995.
APS Manuscript Number C222-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.