Nitric Oxide Induces Heme Oxygenase-1 Gene Expression and Carbon Monoxide Production in Vascular Smooth Muscle Cells

Houston VA Medical Center, TX 77030, USA.
Circulation Research (Impact Factor: 11.02). 05/1997; 80(4):557-64. DOI: 10.1161/01.RES.80.4.557
Source: PubMed


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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    • "159] CNCSIS-UEFISCSU and CARDIOPRO project ID:143, ERDF co-financed investment in RTDI for Competitiveness. to regulate vascular reactivity and blood pressure (Durante et al. 1997). Caveolae have been implicated in chronic inflammatory conditions and other pathologies including atherosclerosis, pulmonary dysfunctions, inflammatory bowel disease, muscular dystrophy and generalized dyslipidemia (Simionescu and Simionescu 1991; Simionescu and Antohe 2006; Chidlow and Sessa 2010; Uyy et al. 2010). "
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    • "Although CO activates cGMP, nitric oxide (NO) activates it more potently [144]. The relationship between these two molecules seems to involve a complex negative feedback loop: NO induces HO-1 expression and consequently CO production [145], while conversely, HO-1 and CO inhibit NO synthesis activity [146,147]. "
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    01/2013; 3(1):1. DOI:10.1186/2045-9912-3-1
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