Effect of mechanical strain on expression of Na+,K+-ATPase alpha subunits in rat aortic smooth muscle cells.
This article reviews related studies from the authors' laboratory, which focus on the regulation of vascular Na+,K+-ATPase in hypertension. Earlier studies, including the authors', suggested that Na-pump activity in cardiovascular tissues is subject to regulation during hypertension; most of these studies report a stimulation of the vascular enzyme during established stages of hypertension. To test hypothesis that in vascular smooth muscle, strain resulting from elevated pressure may be a signal initiating a cascade of events leading to increased expression of Na+,K+-ATPase, the authors used cell culture and the Flexercell Strain Unit to apply cyclical stretch to rat aortic smooth muscle cells (ASMC) for several days. These studies demonstrated that mechanical strain induces the upregulation of both the alpha-1 and alpha-2 subunits of Na+,K+-ATPase. Mechanisms underlying these changes appear to involve a transient increase in intracellular sodium entering the cell through stretch-activated channels. Calcium entering the cell via L-type channels did not affect stretch-induced upregulation of the alpha isoforms. In addition, protein kinase C inhibition resulted in inhibition of the Na-pump during stretch, but not under nonstretch conditions. The authors conclude that the stretch component of vascular pressure upregulates the Na+,K+-ATPase catalytic subunits. Intracellular sodium may be a signal for this regulation. In addition, phosphorylation by PKC may be important in stretch-induced short-term regulation of the vascular Na-pump.
Songu-Mize
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Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112, USA. emize@lsumc.edu
Liu
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Hymel
L J
LJ
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D002478:Cells, Cultured; D006973:Hypertension / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D010446:Peptide Fragments / Q000096:biosynthesis*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000737:chemistry; D013314:Stress, Mechanical; D015854:Up-Regulation
D010446:Peptide Fragments; D000254:Sodium-Potassium-Exchanging ATPase