Cigarette smoke-induced endothelium dysfunction: role of superoxide anion

Objectives Cigarette smoking is strongly associated with coronary artery di sease and atherosclerosis, While smoking has been shown to impair endotheli um-dependent vasorelaxation, the mechanisms involved are not completely und erstood, We investigated the role of superoxide anion and vasoconstricting prostanoids in cigarette smoke induced endothelial dysfunction. Methods Endothelial function was assessed in rat aortic rings exposed to ci garette smoke-treated Krebs buffer, by measuring agonist stimulated endothe lium-dependent vasorelaxation, Treatment with superoxide dismutase (SOD) as well as ifetroban, thromboxane A(2)/prostaglandin endoperoxide H-2 (TXA(2) /PGH(2)) receptor blocker and indomethacin (cyclooxygenase inhibitor) was u sed to investigate the role of superoxide anion and vasoconstricting eicosa noids on cigarette smoke-induced endothelial dysfunction, The effect of cig arette smoke on endothelial nitric oxide synthase (eNOS) catalytic activity was measured by conversion of L-arginine to L-citrulline in rat aortas and rat endothelial cell homogenates supplemented with eNOS cofactors. Results Relaxations to receptor-dependent agonists, acetylcholine and adeno sine diphosphate (ADP), as well as to a receptor-independent agonist, A2318 7 (Ca2+ ionophore) were significantly impaired by cigarette smoke. Cigarett e smoke did not impair relaxations to sodium nitroprusside, indicating pres erved guanylate cyclase activity. Further, cigarette smoke did not affect e NOS catalytic activity in homogenates from either endothelial cells or aort as previously exposed to cigarette-smoke-treated Krebs buffer, Treatment wi th SOD or ifetroban and in a lesser degree by indomethacin prevented cigare tte-smoke-induced endothelial dysfunction. Conclusions Taken together, our results suggest that cigarette smoking caus es an increase in vascular superoxide production which results in decreased nitric oxide (NO) bioactivity and concomitantly increases production of cy clooxygenase dependent and independent vasoconstricting eicosanoids. J Hype rtens 19:891-897 (C) 2001 Lippincott Williams & Wilkins.