Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats.

Abstract

Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes [monocyte infiltration into coronary vessels, nuclear factor-kappaB (NF-kappaB) activation, and monocyte chemoattractant protein-1 expression] as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, no direct evidence for the importance of NF-kappaB in this process is known. We examined the effect of a cis element decoy strategy to address the functional importance of NF-kappaB in the pathogenesis of cardiovascular remodeling. We found here that in vivo transfection of cis element decoy oligodeoxynucleotides against NF-kappaB to hearts prevented the L-NAME-induced early inflammation and subsequent coronary vascular medial thickening. In contrast, NF-kappaB decoy oligodeoxynucleotide transfection did not decrease the development of fibrosis, the expression of transforming growth factor-beta(1) mRNA, or systolic pressure overload induced by L-NAME administration. The NF-kappaB system participates importantly in the development of early vascular inflammation and subsequent medial thickening but not in fibrogenesis in this model. The present study may provide a new aspect of how endothelium-derived NO contributes to anti-inflammatory and/or antiarteriosclerotic properties of the vascular endothelium in vivo.