Sorajja Paul, Cable David G, Hamner Chad E, Schaff Hartzell V
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
J Surg Res. 2004 Sep;121(1):38-41. doi: 10.1016/j.jss.2004.03.022.
Although the anticoagulatory properties of hirudin are well known, its direct vasoactive effects have not been investigated extensively. Hirudin stimulates nitric oxide and prostacyclin production in noncoronary vascular beds, but its actions on coronary arteries are unknown.
Five-millimeter segments of canine left circumflex coronary arteries were obtained for organ chamber experiments. Some segments were denuded of endothelium before study. Segments were exposed to hirudin (10(-10)-10(-6) mol/L) following precontraction with prostaglandin F(2alpha) with or without pretreatment with indomethacin or calcium channel blockers (verapamil and nifedipine).
Hirudin stimulated endothelium-independent contraction in coronary arterial segments. Maximum tension (hirudin 10(-6) mol/L) above precontraction baseline was 33.6 +/- 9.0% (n = 10, P < 0.05) for endothelium-intact and 31.8 +/- 11.5% (n = 8, P < 0.05) for endothelium-denuded arterial segments. Differences between endothelium-intact and endothelium-denuded segments were not significant. Contractile responses to hirudin were unaffected by the presence of indomethacin. Pretreatment with either verapamil or nifedipine (10(-4) mol/L) for 1 h attenuated these contractions. The maximal increase in tension above baseline (hirudin 10(-6) mol/L) for verapamil and nifedipine was only 6.2 +/- 12.4 and 3.8 +/- 7.0% (n = 6, P < 0.05 versus endothelium-intact control), respectively.
Hirudin stimulates endothelium-independent contractions of canine coronary arteries in vitro. Pretreatment with calcium channel blockers attenuates this response, suggesting that extracellular influx of calcium has an important mechanistic role in hirudin-mediated coronary artery constriction.
尽管水蛭素的抗凝特性已广为人知，但其直接的血管活性作用尚未得到广泛研究。水蛭素可刺激非冠状动脉床中一氧化氮和前列环素的生成，但其对冠状动脉的作用尚不清楚。
获取犬左旋冠状动脉的5毫米节段用于器官腔室实验。部分节段在研究前去除内皮。在用前列腺素F(2α)预收缩后，将节段暴露于水蛭素（10(-10)-10(-6)摩尔/升），同时或不使用吲哚美辛或钙通道阻滞剂（维拉帕米和硝苯地平）进行预处理。
水蛭素刺激冠状动脉节段的非内皮依赖性收缩。对于内皮完整的节段，收缩后基线以上的最大张力（水蛭素10(-6)摩尔/升）为33.6±9.0%（n = 10，P < 0.05），对于内皮剥脱的动脉节段为31.8±11.5%（n = 8，P < 0.05）。内皮完整节段和内皮剥脱节段之间的差异不显著。吲哚美辛的存在不影响对水蛭素的收缩反应。用维拉帕米或硝苯地平（10(-4)摩尔/升）预处理1小时可减弱这些收缩。维拉帕米和硝苯地平处理后，基线以上张力的最大增加（水蛭素10(-6)摩尔/升）分别仅为6.2±12.4%和3.8±7.0%（n = 6，与内皮完整对照相比，P < 0.05）。
水蛭素在体外刺激犬冠状动脉的非内皮依赖性收缩。钙通道阻滞剂预处理可减弱这种反应，表明细胞外钙内流在水蛭素介导的冠状动脉收缩中起重要机制作用。
