Wang J X, Ikomi F, Ohhashi T
1st Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Can J Physiol Pharmacol. 1997 May;75(5):357-62.
The mode of action of 5-hydroxytryptamine (5HT) was investigated in isolated dog anterior spinal small arteries. Lower concentrations of 5HT (10(-9)-10(-7) M) caused a dose-dependent contraction and higher concentrations (10(-6)-10(-3) M) produced a dose-dependent relaxation of the arteries precontracted by 10(-7) M U 46619. The 5HT-induced relaxation was significantly antagonized by methiothepin (10(-9)-10(-6) M). Ketanserin (10(-6) M) and ICS 205-930 (3 x 10(-6) M) did not affect the 5HT-induced relaxation of the arteries. The relaxant response to 5HT was reduced significantly by mechanical rubbing of the endothelial cells. The 5HT-induced endothelium-independent relaxation was also antagonized significantly by methiothepin (10(-6) M). Aspirin (5 x 10(-5) M) or N omega-nitro-L-arginine methyl ester (L-NAME) (10(-6) M) significantly suppressed the 5HT-induced endothelium-dependent relaxation. L-Arginine (10(-3) M) also significantly reversed the L-NAME induced reduction of the 5HT-induced endothelium-dependent relaxation. Treatment with L-NAME in the presence of aspirin also produced much greater reduction of the 5HT-induced endothelium-dependent relaxation. Isocarbacyclin (10(-9)-10(-5) M) induced a concentration-dependent relaxation of the isolated spinal small arteries precontracted by 10(-7) M U 46619. These results suggest that 5HT induces endothelium-dependent and -independent relaxations of the isolated anterior spinal small arteries mainly via activation of 5HT1-like receptor and that endogenous nitric oxide and vasodilative prostaglandins may contribute to the 5HT-induced endothelium-dependent relaxation of the arteries.
在离体犬脊髓前小动脉中研究了5-羟色胺（5HT）的作用方式。较低浓度的5HT（10^(-9)-10^(-7)M）引起剂量依赖性收缩，而较高浓度（10^(-6)-10^(-3)M）则使由10^(-7)M U 46619预收缩的动脉产生剂量依赖性舒张。5HT诱导的舒张被甲硫噻平（10^(-9)-10^(-6)M）显著拮抗。酮色林（10^(-6)M）和ICS 205-930（3×10^(-6)M）不影响5HT诱导的动脉舒张。机械摩擦内皮细胞可显著降低对5HT的舒张反应。5HT诱导的非内皮依赖性舒张也被甲硫噻平（10^(-6)M）显著拮抗。阿司匹林（5×10^(-5)M）或Nω-硝基-L-精氨酸甲酯（L-NAME）（10^(-6)M）显著抑制5HT诱导的内皮依赖性舒张。L-精氨酸（10^(-3)M）也显著逆转了L-NAME诱导的5HT诱导的内皮依赖性舒张的降低。在阿司匹林存在下用L-NAME处理也使5HT诱导的内皮依赖性舒张降低得更多。异卡波前列素（10^(-9)-10^(-5)M）诱导由10^(-7)M U 46619预收缩的离体脊髓小动脉产生浓度依赖性舒张。这些结果表明，5HT主要通过激活5HT1样受体诱导离体脊髓前小动脉的内皮依赖性和非内皮依赖性舒张，并且内源性一氧化氮和血管舒张性前列腺素可能参与5HT诱导的动脉内皮依赖性舒张。
