Effect of nicotine on prostacyclin formation in rat aorta

The effect of nicotine on the formation of 6-keto-prostaglandin F 1α (6-keto-PGF 1α), a metabolite of prostacyclin (PGI 2), in the rat aorta was investigated. Slices of rat aorta were incubated with [ 14C]arachidonic acid ([ 14C]AA) or 14C-labelled prostaglandin endoperoxide H 2 ([ 14C]PGH 2) in the presence of nicotine (2 × 10 −7−2 × 10 −4 M) or indomethacin (2 × 10 −7−2 × 10 −5 M). 14C-Labelled products formed during the incubations were separated and quantified using thin layer chromatography and liquid scintillation spectrometry. A time- and substrate concentration-dependent formation of [ 14C]6-keto-PGF 1α from [ 14C]AA was found in the incubations. The K M of AA for the formation of 6-keto-PGF 1α was 1.3 × 10 −8 M. Nicotine competitively inhibited the formation of [ 14C]6-keto-PGF 1α from [ 14C]AA, the I 50 being about 2 × 10 −4 M. Indomethacin also decreased the formation of [ 14C]keto-PGF 1α from [ 14C]AA, with an I 50 of about 10 −6 M. Incubation of rat aorta slices with [ 14C]PGH 2 also elicited the formation of[ 14C]6-keto-PGF 1α. This conversion was not affected by nicotine. It is concluded that nicotine inhibits the formation of PGI 2 in the rat aorta by competitive inhibition of the cyclo-oxygenase that converts arachidonate to prostaglandin endoperoxide. Furthermore, the data demonstrate that nicotine does not affect PGI 2 synthetase in this tissue.