Cigarette smoke extracts, but not nicotine, inhibit prostacyclin (PGI₂) synthesis in human, rabbit and rat vascular tissue

Ethanolic and aqueous cigarette smoke extracts were tested for their influence on prostacyclin (PGI₂) synthesis in four vascular models: human umbilical artery, rabbit aorta, rat aorta and rat lung. Nicotine was also studied. In each tissue, a dose-dependent inhibition of the release of PGI₂ (assessed by measurement of immunoreactive 6-oxo-PGF_1α, the stable hydrolysis product of PGI₂), was seen on incubation with aqueous or ethanolic cigarette smoke extracts; nicotine, at concentrations of up to 1 g/1, was without effect. In vitro conversion of [¹⁴C]-arachidonic acid to [¹⁴C]-6-oxo-PGF_1α by human umbilical artery was also inhibited by both ethanolic and aqueous cigarette smoke extracts, whereas nicotine was again without effect. We conclude that cigarette smoke inhibits PGI₂ synthesis at the level of cyclooxygenase or beyond it, and that components other than nicotine are responsible for this effect. In blood vessels, the inhibition of PGI₂ synthesis may contribute to the pathogenesis of the vascular complications of smoking.