Murohara T, Kugiyama K, Sugiyama S, Ohgushi M, Yasue H
Division of Cardiology, Kumamoto University School of Medicine, Japan.
J Cardiovasc Pharmacol. 1993 May;21(5):760-6. doi: 10.1097/00005344-199305000-00011.
Interaction between activated human polymorphonuclear leukocytes (PMNL) and endothelial regulation of isolated pig coronary artery tone was examined. PMNL were isolated from venous blood of healthy human volunteers. Pig coronary artery rings were incubated in an organ chamber, and isometric tension changes induced by opsonized zymosan (1 mg/ml)-activated PMNL were examined. Activated PMNL elicited dose-dependent contraction (maximum value 45.9 +/- 4.1% of precontraction, mean +/- SEM] in prostaglandin F2 alpha (PGF2 alpha)-precontracted rings. The contraction was markedly attenuated by superoxide dismutase (SOD 100 U/ml) to 9.9 +/- 2.4% (p < 0.001), but not by catalase (1,000 U/ml). After inhibition of basal production of endothelium-derived relaxing factor (EDRF) (nitric oxide, NO) by endothelial removal or by treatment of an inhibitor of NO synthase, NG-monomethyl-L-arginine (L-NMMA), PMNL also failed to induce the contraction. A 5-lipoxygenase inhibitor (AA-861) and a cyclooxygenase inhibitor (indomethacin) did not alter the contraction to activated PMNL significantly. Time course of oxygen free radical release from PMNL measured by luminol-dependent chemiluminescence was closely synchronized with that of the endothelium-dependent contraction elicited by PMNL. In each preparation of PMNL, the maximum luminescence count and the maximum contraction induced by activated PMNL showed significant positive correlation quantitatively (r = 0.958, p < 0.001). Activated human PMNL elicited endothelium-dependent contraction in isolated pig coronary arteries. The contraction may be mediated through inactivation of basal production of EDRF (NO) by superoxide anions released from PMNL.
研究了活化的人多形核白细胞（PMNL）与离体猪冠状动脉张力的内皮调节之间的相互作用。从健康人类志愿者的静脉血中分离出PMNL。将猪冠状动脉环置于器官浴槽中，检测经调理酵母聚糖（1mg/ml）活化的PMNL诱导的等长张力变化。活化的PMNL在前列腺素F2α（PGF2α）预收缩的环中引起剂量依赖性收缩（最大值为收缩前的45.9±4.1%，平均值±标准误）。超氧化物歧化酶（SOD 100U/ml）可使收缩明显减弱至9.9±2.4%（p<0.001），但过氧化氢酶（1000U/ml）则无此作用。通过去除内皮或用一氧化氮合酶抑制剂NG-甲基-L-精氨酸（L-NMMA）处理抑制内皮源性舒张因子（EDRF，一氧化氮，NO）的基础生成后，PMNL也无法诱导收缩。5-脂氧合酶抑制剂（AA-861）和环氧化酶抑制剂（吲哚美辛）对活化PMNL引起的收缩无明显改变。通过鲁米诺依赖性化学发光法测定的PMNL释放氧自由基的时间进程与PMNL引起的内皮依赖性收缩的时间进程密切同步。在每种PMNL制剂中，活化的PMNL诱导的最大发光计数与最大收缩在数量上呈显著正相关（r=0.958，p<0.001）。活化的人PMNL在离体猪冠状动脉中引起内皮依赖性收缩。这种收缩可能是通过PMNL释放的超氧阴离子使EDRF（NO）的基础生成失活介导的。
