NONOates regulate KCl cotransporter-1 and -3 mRNA expression in vascular smooth muscle cells

Departments of 1  Pharmacology and Toxicology, 2  Physiology and Biophysics, and 3  Cardiology, School of Medicine, Wright State University, Dayton, Ohio 45435-0002 Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep er...

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Published in:American journal of physiology. Heart and circulatory physiology 2003-05, Vol.284 (5), p.H1686-H1692
Main Authors: Di Fulvio, Mauricio, Lauf, Peter K, Shah, Shalin, Adragna, Norma C
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Gene Expression - drug effects
Guanylate Cyclase
K Cl- Cotransporters
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - physiology
Nitric Oxide - metabolism
Nitric Oxide Donors - pharmacology
Nitroso Compounds - pharmacology
Rats
Receptors, Cytoplasmic and Nuclear - metabolism
RNA, Messenger - analysis
Soluble Guanylyl Cyclase
Symporters - genetics
Triazenes - pharmacology
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Summary:Departments of 1  Pharmacology and Toxicology, 2  Physiology and Biophysics, and 3  Cardiology, School of Medicine, Wright State University, Dayton, Ohio 45435-0002 Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep erythrocytes and in primary cultures of rat vascular smooth muscle cells (VSMCs), respectively. In this study, we used NONOates as rapid and slow NO releasers to provide direct evidence implicating NO as a regulator of KCC3 gene expression at the mRNA level. In addition, we used the expression of KCC3 mRNA to further investigate the mechanism of action of these NO donors at the cellular level. Treatment of VSMCs with rapid NO releasers, like NOC-5 and NOC-9, as well as with the direct NO-independent soluble guanylyl cyclase (sGC) stimulator YC-1, acutely increased KCC3 mRNA expression in a concentration- and time-dependent manner. The slow NO releaser NOC-18 had no effect on KCC3 gene expression. A specific NO scavenger completely prevented the NONOate-induced KCC3 mRNA expression. Inhibition of sGC with LY-83583 blocked the NONOate- and YC-1-induced KCC3 mRNA expression. This study shows that in primary cultures of rat VSMCs, the fast NO releasers NOC-9 and NOC-5, but not the slow NO releaser NOC-18, acutely upregulate KCC3 mRNA expression in a NO/sGC-dependent manner. nitric oxide; soluble guanylyl cyclase
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00710.2002