Kiyoshi Akihiko, Ishikawa Tomohisa, Hayashi Ken-ichi, Iwatsuki Yoshiyuki, Ishii Kunio, Nakayama Koichi
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City, Shizuoka 422-8526, Japan.
Pflugers Arch. 2003 Nov;447(2):142-9. doi: 10.1007/s00424-003-1159-z. Epub 2003 Sep 27.
Rhythmical contractions accompanied by an increase in cytosolic Ca2+ concentrations were produced in ring preparations of endothelium-denuded pulmonary arteries from monocrotaline-treated rats, but not in those from vehicle-treated rats, 2-3 h after a resting tension of 15 mN (150-180% of the initial wall length of the artery) was applied. The rhythmical contractions were abolished by nicardipine and ryanodine. Cyclopiazonic acid reduced the relaxation phase of the rhythmical contractions, finally leading to a sustained contraction. Similarly, apamin caused a sustained contraction, whereas charybdotoxin increased the amplitude of the rhythmical contractions. Glibenclamide had no apparent effects on them. Indomethacin and the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 abolished the rhythmical contractions and reduced the tension, but the thromboxane synthase inhibitor ozagrel had no effect. These results suggest that optimal stretch induces rhythmical contractions in the pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats, to which both Ca2+ influx through voltage-operated Ca2+ channels and Ca2+ release from the endoplasmic reticulum seem to contribute. It is also suggested that small-conductance Ca(2+)-activated K+ channels participate in the relaxation phase of rhythmical contractions. Furthermore, prostaglandin H2 released from nonendothelial cells is likely to play a pivotal role in the induction of rhythmical contractions.
在施加15 mN（动脉初始壁长的150 - 180%）的静息张力2 - 3小时后，从接受野百合碱处理的大鼠获取的去内皮肺动脉环标本中产生了伴有胞质Ca2+浓度升高的节律性收缩，但在接受溶剂处理的大鼠的标本中未出现这种情况。尼卡地平和ryanodine可消除节律性收缩。环匹阿尼酸减少了节律性收缩的舒张期，最终导致持续收缩。同样，蜂毒明肽引起持续收缩，而大蝎毒素增加了节律性收缩的幅度。格列本脲对它们没有明显影响。吲哚美辛和前列腺素H2/血栓素A2受体拮抗剂SQ29548消除了节律性收缩并降低了张力，但血栓素合酶抑制剂奥扎格雷没有作用。这些结果表明，最佳拉伸可诱导野百合碱诱导的肺动脉高压大鼠的肺动脉产生节律性收缩，电压门控Ca2+通道的Ca2+内流和内质网的Ca2+释放似乎都对此有贡献。还表明小电导Ca(2+)-激活K+通道参与了节律性收缩的舒张期。此外，从非内皮细胞释放的前列腺素H2可能在节律性收缩的诱导中起关键作用。
