Regulation of Nitric Oxide Synthase Induction in Cultured Vascular Smooth Muscle Cells by Lipopolysaccharide and Interferon

Abstract

Nitric oxide is synthesized by vascular smooth muscle cells in response to endotoxin or inflammatory mediators. We investigated the molecular basis for the induction of nitric oxide synthase (NOS) in response to lipopolysaccharide (LPS) or IL-1β using rat vascular smooth muscle cells derived from pulmonary and systemic vasculature. The regulation of mRNA levels for this enzyme in response to LPS or IL-1β treatment was examined in parallel with changes in levels of cyclic GMP. We found an increase in expression of inducible NOS transcript corresponding to an increase in cyclic GMP levels beginning with 3 hr of exposure to either LPS or IL-Iβ. In cells derived from the pulmonary circulation, initial induction of NOS transcript was detectable at 3 hr and the transcript levels continued to increase to a maximum level at 24 hr. In contrast, the cells derived from the systemic vasculature showed a maximal induction of NOS transcript at 3 hr, and the level decreased from this time point to 24 hr. The full induct...