喫煙のラット血小板thromboxane A2（TXA2）および大動脈prostacyclin（PGI2）産生に与える効果について

Effect of cigarette smoking on platelet-thromboxane A2 and arterial-prostacyclin synthesis in rats

　血小板で産生されるCyclooxygenase代謝物throm-boxane A₂（TXA₂）は強力な血小板凝集作用と血管平滑筋収縮作用を有し，血管内血栓形成に主要な役割を果たしている^1）。血小板にはさらに高い12-lipoxygenase活性があることが知られていたが^2），その産物の臨床意義は不明であった。近年12-hydroxyeicosatetraenoicacid （12-HETE）が白血球遊走のみならず，強力な平滑筋細胞の遊走をひきおこすことが報告され^3〜5），血栓形式にひきつづき生ずる動脈硬化を含めた慢性の血管障害にTXA₂とともに重要な役割を果たしている可能性が示された。一方動脈内皮細胞で産生されるprostaglan-din I₂（PGI₂）は強力な抗血小板凝集抑制作用と，血管拡張作用を有し，血管病変の進行を抑制している可能性が考えられている^1）。

　喫煙は動脈硬化，血栓をひきおこし，狭心症，心筋梗塞脳血管障害の発症に対して重大な危険因子のひとつであることはよく知られているが，その明確なメカニズムは不明である。

It has been considered that cigarette smoking causes atherosclerotic change in arteries by altering enzyme activities of metabolic pathway of arachido-nic acid in platelets and arterial endothelium. We previously repored that cigarette smoking stimulated synthesis of 12-hydroxyeicosatetraenoic acid (12-HATE), but not of thromboxane A₂ (TXA₂) in pla-telets of rats grown under smoking condition for 4 and 8 weeks.

In this study, we reexamined the effect of ciga-rette smoking on the synthesis of TXA₂ in platelets of rats grown under smoking condition for 8 and 13 weeks. We also examined the effect of smoking on synthesis of prostacyclin (PGI₂) in thoracic arte-rial strips of the same rats. Smoking for 13 as well as 8 weekes gave no significant effects on the syn-thesis of TXA₂ in platelets or the synthesis of PGI₂ in arterial strips. However, synthesis of 6- keto PGF_1α was significantly lower in arterial strips from smoking rats for 13 weeks than those from smoking rats for 8 weeks, suggesting that aging was an important factor affecting synthesis of PGI₂ in arterial endothelium. There was no significant dif-ference in TXA₂ synthesis in platelets between smoking rats for 8 weeks and those for 13 weeks.