INDUCTION OF ENDOTHELIAL-CELL INJURY BY CIGARETTE-SMOKE

Cigarette smoke contains different populations of free radicals which may be responsible for endothelial cell (EC) injury of smokers, The pu rpose of this study was to examine the effects of gas-phase cigarette smoke on EC endothelium-derived relaxing factor (EDRF)/NO-guanylate cy clase (GC)-cGMP pathway and on EC detatchment-type injury after incuba tion with smoke. Furthermore, we examined whether different kind of an tioxidants can prevent smoke-caused EC injury. We measured cGMP pathwa y using direct (sodium nitroprusside, SNP) and indirect (A23187, the c alcium ionophore and bradykinin, BK) activators of GC, Directly and in directly stimulated EC cGMP production dose-dependently decreased and EC detatchment increased after incubation with smoke. Externally added thiols (glutathione, GSH; D-Penicillamine, DP; N-acetyl-cysteine, NAC ) protected EC from damage of cGMP production and cell detatchment. Ot her antioxidants (catalase, deferoxamine and superoxide dismutase) wer e ineffective. These results suggest that the thiol containing GC in E C is destroyed or inactivated or thiol like species responsible for ac tivation of GC is incomplete in EC after incubation with smoke. It is also possible that externally added thiols bind an unknown component o f smoke and this way, EC is protected. EC injury may contribute to vas cular diseases associated with cigarette smoking.