强啡肽抑制离体血管收缩效应的机制

用离体血管电场刺激收缩模型观察到强啡肽明显抑制电场刺激引起的兔耳中心动脉及兔肠系膜上动脉的收缩效应,且呈剂量反应关系,而对股动脉的电场刺激收缩反应无明显影响,强啡肽抑制血管收缩达50％时的用量(IC_(50)值)分别为8.5±1.2×10~(-6)mol/L、5.02±1.3×10~(-7)mol/L及>10~(-6)mol/L。 用药物分析法看到,酚妥拉明(10~(-6)mol/L)可取消电场刺激及去甲肾上腺素引起的血管收缩作用,而强啡肽仅抑制电场刺激致血管收缩作用。 用HPLC法测定孵育液中去甲肾上腺素的含量变化时看到,应用强啡肽(5×10~(-7)mol/L)后孵育液中去甲肾上腺素的含量从对照组的340.56±73.13pg/ml下降至67.91±10.26pg/ml,两组差别有极显著意义(P<0.01)。纳洛酮(10~(-6)mol/L)可完全拮抗强啡肽的这一抑制效应。 以上结果提示强啡肽可能通过抑制交感神经末梢释放去甲肾上腺素,从而产生抑制血管的收缩作用。

MECHANISM OF DYNORPHIN INHIBITION ON VASOCONSTRICTION IN VITRO

Bioassay and HPLC detection were used to analyze the mechanism of inhibition of stimulation-induced vasoconstriction by dynorphin 1-13 (D1-13). Bioassay showed that D1-13 inhibited the contraction of rabbit ear artery and mesenteric artery induced by electrical field stimulation with IC50s of 8.5 +/- 1.2 x 10(-8) mol/L (n = 4) and 5.02 +/- 1.3 x 10(-7) mol/L (n = 5), respectively. D1-13 was ineffective in rabbit femoral artery at a concentration even larger than 10(-6) mol/L. D1-13 did not alter the basal tension of the blood vessel, nor the vasoconstriction induced by adding norepinephrine (NE) into the bath medium, and both constriction were markedly inhibited by phentolamine, an alpha-adrenoceptor blocker. With HPLC detection, the contents of NE in the bath medium were significantly reduced by D1-13 (5 x 10(-7) mol/L) from 340.56 +/- 73.13 pg/ml to 76.91 +/- 10.26 pg/ml as compared with control group (P less than 0.05). The effect could be completely reversed by naloxone at a concentration of 10(-6) mol/L (P less than 0.05). The results suggest that D1-13 reduces stimulation-induced vasoconstriction probably through a presynaptic inhibition of NE release from the nerve terminals.