AJP - Cell Physiology, Vol 269, Issue 4 C884-C891, Copyright © 1995 by American Physiological Society
cAMP evokes a rise in intracellular Na+ mediated by Na+ pump inhibition in rat aortic smooth muscle cells
M. L. Borin
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
The effect of adenosine 3',5'-cyclic monophosphate (cAMP) on intracellular
Na+ concentration ([Na+]i) was studied in primary cultured vascular smooth
muscle cells from rat aorta. [Na+]i was measured using digital imaging of
cells loaded with the Na(+-)sensitive fluorescent dye sodium-bonding
benzofuran isophthalate. The cAMP level was raised by 1) the
membrane-permeable cAMP derivative 8-bromoadenosine 3',5'-cyclic
monophosphate, 2) the combination of the adenylate cyclase activator
forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine,
and 3) the beta-adrenoceptor agonist isoproterenol. All three methods
caused a dose-dependent continuous rise in [Na+]i during 40-60 min of
observations. A rise in [Na+]i may be caused by stimulation of the Na+
influx and/or inhibition of Na+ efflux; therefore, the involvement of both
mechanisms was studied. Elevation of the cAMP level had no effect on Na+
influx, measured as the rate of rise of [Na+]i when Na+ efflux was
inhibited with 1 mM ouabain. In contrast, elevation of the cAMP level
attenuated Na+ efflux, measured as the rate of decline of [Na+]i in
Na(+)-loaded cells exposed to Na(+)-free medium. cAMP-induced inhibition of
Na+ efflux was not observed when the Na+ pump was inhibited; therefore,
cAMP inhibits the Na+ pump-mediated component of Na+ efflux. Agents that
raise the cAMP level also inhibited, in a dose-dependent fashion,
ouabain-sensitive 86Rb uptake in rat aortic rings. The latter observation
confirms that the cAMP-induced inhibition of the Na+ pump occurs both in
cultured cells and in the native tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
