9118487

pubmed:Citation

4

Since recent studies demonstrate that vascular smooth muscle cells synthesize two distinct guanylate cyclase-stimulatory gases, NO and CO, we examined possible regulatory interactions between these two signaling molecules. Treatment of rat aortic smooth muscle cells with the NO donors, sodium nitroprusside, S-nitroso-N-acetyl-penicillamine, or 3-morpholinosydnonimine, increased heme oxygenase-I (HO-1) mRNA and protein levels in a concentration and time-dependent manner. Both actinomycin D and cycloheximide blocked NO-stimulated HO-1 mRNA and protein expression. Nuclear run-on experiments demonstrated that NO donors increased HO-1 gene transcription between 3- and 6-fold. In contrast, NO donors had no effect on the stability of HO-1 mRNA. Incubation of vascular smooth muscle cells with the membrane-permeable cGMP analogues, dibutyryl cGMP and 8-bromo-cGMP, failed to induce HO-1 gene expression. Treatment of vascular smooth muscle cells with NO donors also stimulated the production and release of CO, as demonstrated by the CO-dependent increase in intracellular cGMP levels in coincubated platelets. Finally, incubating vascular smooth muscle cells with interleukin-1 beta and tumor necrosis factor-alpha induced NO synthesis and also significantly increased the level of HO-1 protein. The cytokine-stimulated production of both NO and HO-1 protein in smooth muscle cells was blocked by the NO synthase inhibitor methyl-L-arginine. These results demonstrate that exogenously administered or endogenously released NO stimulates HO-1 gene expression and CO production in vascular smooth muscle cells. The ability of NO to induce HO-catalyzed CO release from vascular smooth muscle cells provides a novel mechanism by which NO might modulate soluble guanylate cyclase and, thereby, vascular smooth muscle cell and platelet function.

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MEDLINE

0009-7330

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557-64

pubmed-meshheading:9118487-Animals, pubmed-meshheading:9118487-Carbon Monoxide, pubmed-meshheading:9118487-Cells, Cultured, pubmed-meshheading:9118487-Cyclic GMP, pubmed-meshheading:9118487-Cycloheximide, pubmed-meshheading:9118487-Cytokines, pubmed-meshheading:9118487-Dactinomycin, pubmed-meshheading:9118487-Enzyme Inhibitors, pubmed-meshheading:9118487-Gene Expression Regulation, pubmed-meshheading:9118487-Heme Oxygenase (Decyclizing), pubmed-meshheading:9118487-Molsidomine, pubmed-meshheading:9118487-Muscle, Smooth, Vascular, pubmed-meshheading:9118487-Nitric Oxide, pubmed-meshheading:9118487-Nitroprusside, pubmed-meshheading:9118487-Penicillamine, pubmed-meshheading:9118487-RNA, Messenger, pubmed-meshheading:9118487-Rats, pubmed-meshheading:9118487-S-Nitroso-N-Acetylpenicillamine, pubmed-meshheading:9118487-Time Factors, pubmed-meshheading:9118487-Transcription, Genetic

Nitric oxide induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't