1. The changes in plasma levels of thromboxane-B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) were examined in rats given 5, 25, 50 or 100 micrograms/mL nicotine in drinking water for 10 days. 2. The effect of nicotine on prostacyclin (PGI2) synthesis from endogenous arachidonic acid by cultured rabbit aortic smooth muscle cells was also studied. 3. Plasma levels of TXB2 were increased dose-dependently by treatment for 10 day with nicotine. 4. 6-Keto-PGF1 alpha values were lowered dose-dependently, both in the plasma of nicotine-treated rats and in rabbit aortic smooth muscle cells incubated with the alkaloid. 5. The results suggest that endogenous synthesis of thromboxane-A2 and PGI2, as reflected by TXB2 and 6-keto-PGF1 alpha levels, respectively, is influenced by nicotine treatment. These findings may be related to cardiovascular diseases associated with cigarette smoking, but further studies are needed.

Glibenclamide is a sulfonylurea used in the management of diabetes mellitus but which is also known to have antagonist activity against the effects of some eicosanoids on smooth muscle. We have examined the action of glibenclamide against contractions of rings of canine middle cerebral artery by prostaglandins F_2α, E₂ and D₂ and the thromboxane A₂ analog U46619. All these responses were significantly attenuated by glibenclamide, while contractions to potassium chloride, noradrenaline, 5-hydroxytryptamine or caffeine were unaffected. The effects of glibenclamide against the vascular actions of oxyhemoglobin were also examined, since this agent is believed to be responsible for the vasospasm which follows subarachnoid hemorrhage. Contractions to oxyhemoglobin were significantly inhibited by glibenclamide, which suggests that at least part of the contractile effects of oxyhemoglobin in cerebral arteries is mediated by eicosanoids. Glibenclamide is thus an agent which selectively blocks the contractile effects of both eicosanoids and oxyhemoglobin.