Cigarette smoke-induced endothelium dysfunction: Role of superoxide anion

Leopoldo Raij, Eugene G. DeMaster, Edgar A. Jaimes

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Objectives. Cigarette smoking is strongly associated with coronary artery disease and atherosclerosis. While smoking has been shown to impair endothelium-dependent vaso relaxation, the mechanisms involved are not completely understood. 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 cigarette smoke-treated Krebs buffer, by measuring agonist stimulated endothelium-dependent vasorelaxation. Treatment with superoxide dismutase (SOD) as well as ifetroban, thromboxane A2/prostaglandin endoperoxide H2 (TxA2/PGH2) receptor blocker and indomethacin (cyclooxygenase inhibitor) was used to investigate the role of superoxide anion and vasoconstricting eicosanoids on cigarette smoke-induced endothelial dysfunction. The effect of cigarette 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 adenosine diphosphate (ADP), as well as to a receptor-independent agonist, A23187 (Ca2+ ionophore) were significantly impaired by cigarette smoke. Cigarette smoke did not impair relaxations to sodium nitroprusside, indicating preserved guanylate cyclase activity. Further, cigarette smoke did not affect eNOS catalytic activity in homogenates from either endothelial cells or aortas previously exposed to cigarette-smoke-treated Krebs buffer. Treatment with SOD or ifetroban and in a lesser degree by indomethacin prevented cigarette-smoke-induced endothelial dysfunction. Conclusions. Taken together, our results suggest that cigarette smoking causes an increase in vascular superoxide production which results in decreased nitric oxide (NO) bioactivity and concomitantly increases production of cyclooxygenase dependent and independent vasoconstricting eicosanoids.

Original languageEnglish
Pages (from-to)891-897
Number of pages7
JournalJournal of Hypertension
Volume19
Issue number5
DOIs
StatePublished - May 24 2001
Externally publishedYes

Fingerprint

Smoke
Tobacco Products
Superoxides
Endothelium
Nitric Oxide Synthase Type III
Eicosanoids
Smoking
Indomethacin
Superoxide Dismutase
Aorta
Coronary Artery Disease
Buffers
Endothelial Cells
Prostaglandin H2 Receptors Thromboxane A2
Cholinergic Agonists
Citrulline
Thromboxane A2
Cyclooxygenase Inhibitors
Guanylate Cyclase
Ionophores

Keywords

  • Cigarette smoking
  • Nitric oxide
  • Nitric oxide synthase
  • Superoxide anion

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Cigarette smoke-induced endothelium dysfunction : Role of superoxide anion. / Raij, Leopoldo; DeMaster, Eugene G.; Jaimes, Edgar A.

In: Journal of Hypertension, Vol. 19, No. 5, 24.05.2001, p. 891-897.

Research output: Contribution to journalArticle

Raij, Leopoldo ; DeMaster, Eugene G. ; Jaimes, Edgar A. / Cigarette smoke-induced endothelium dysfunction : Role of superoxide anion. In: Journal of Hypertension. 2001 ; Vol. 19, No. 5. pp. 891-897.
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