cAMP evokes a rise in intracellular Na+ mediated by Na+ pump inhibition in rat aortic smooth muscle cells.
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)
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D015124:8-Bromo Cyclic Adenosine Monophosphate; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium