REDUCED GLUTATHIONE PREVENTS NITRIC OXIDE-INDUCED APOPTOSIS IN VASCULAR SMOOTH-MUSCLE CELLS

The control of medial and neointimal growth, in which vascular smooth muscle (VSM) plays a central role, is most important to the developmen t of hypertension and atherosclerosis, respectively. Growth of vascula r smooth muscle cells is regulated by a number of factors, including t he vasodilator nitric oxide (NO). In addition, NO modulates intracellu lar thiol redox states and the thiol redox state of the cell influence s NO production. We, therefore, examined the nature of the effect of N O on growth of VSM cells and its modulation by cellular glutathione co ntent. Here, we report that NO, either generated by NO donors or synth esized by NOS in VSM cells, inhibited DNA synthesis and induced apopto sis in this cell type. NO-induced apoptosis was associated with a sign ificant decrease in the intracellular concentration of reduced glutath ione and with an increase in the level of the tumor suppressor gene p5 3 mRNA. Moreover, addition of glutatkione monoethylester to the cultur e restored the level of reduced glutathione in VSM cells, and prevente d the NO-induced increase in p53 expression and programmed cell death. Our findings suggest a role for reduced glutathione in protecting VSM cells exposed to NO from apoptosis. (C) 1997 Elsevier Science B.V.