Pressure stress reduces inducible NO synthase expression by interleukin-1ß stimulation in cultured rat vascular smooth muscle cells.

Elevated mechanical stress applied to vascular walls is well known to modulate vascular remodeling. We investigated the effect of pulsatile pressure stress on nitric oxide (NO) production and inducible NO synthase (iNOS) expression by interleukin-1ß (IL-1ß) stimulation in rat vascular smooth muscle cells (VSMCs). VSMCs were enzymatically isolated from aortic media of Wistar rats. Pulsatile pressure applied to VSMCs was repeatedly given between 80 and 160 mm Hg at a frequency of 4 cycles per min using an original apparatus. Protein expression and activation were evaluated by Western blot analysis. mRNA expression was evaluated by real-time reverse transcription-polymerase chain reaction. The pulsatile pressure reduced IL-1ß-induced NO production, iNOS protein, and mRNA expression. The pressure also reduced GTP cyclohydrolase I mRNA expression. Furthermore, the pressure reduced phosphorylation of IL-1ß-induced extracellular signal-regulated kinase (ERK), nuclear factor-κB (NF-κB) p65, and I-κBα. The pressure had no effect on I-κBß degradation by IL-1ß stimulation. The present study shows for the first time that pressure stress reduces IL-1ß-induced iNOS expression via a mechanism involving the ERK-NF-κB signaling pathway.