The impaired glutathione system and its up-regulation by sulforaphane in vascular smooth muscle cells from spontaneously hypertensive rats

The glutathione (GSH) system plays an important role in reducing oxidative stress, the increase of which has been linked to the pathogenesis of hypert ension. The aims of this study were to investigate: (1) whether the GSH sys tem was impaired in aortic smooth muscle cells (SMCs) from spontaneously hy pertensive rats (SHR), and (2) whether this system could be up-regulated by the phase-2 enzyme inducers, sulforaphane and t-butylhydroquinone (t-BHQ). Basal levels of cellular GSH, GSH-reductase and GSH-peroxidase were signif icantly lower in SMCs from SHR than from normotensive Wistar-Kyoto (WKY) ra ts. Heme oxygenase-1 (HO-1) was significantly higher in SHR SMCs, which cor related with the higher oxidative stress experienced by these cells. No dif ferences were observed in the basal activity of GSH-S-transferase nor in th e ability to synthesize GSH between SMCs from these two strains. Sulforapha ne (0.05-1 mu mol/1) and t-BHQ (10-100 mu mol/1) induced significant and co ncentration-dependent increases in cellular GSH levels, HO-1 protein conten t and activities of GSH-reductase and GSH-peroxidase in SMCs from both rat strains. Upregulation of phase 2 enzymes correlated with a decrease in oxid ative stress experienced by the SMCs, particularly with SHR. We conclude th at SHR SMCs experience greater oxidative stress than WKY SMCs and that malf unction of the GSH system contributes to the enhanced oxidative stress in S HR SMCs. (C) 2001 Lippincott Williams & Wilkins.