Takizawa T, Horikoshi E, Kamata A
Department of Developmental and Reproductive Biotechnology, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
J Vet Med Sci. 1999 Dec;61(12):1277-80. doi: 10.1292/jvms.61.1277.
The purpose of this study was to examine the role of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) system in the regulation of the ductus arteriosus (DA) patency in fetal rats. Pregnant rats were administered N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg, ip), an NO synthase (NOS) inhibitor; methylene blue (30, 50 and 100 mg/kg, ip), a soluble guanylate cyclase inhibitor; or indomethacin (3 mg/kg, po), a cyclooxygenase inhibitor, at various times before cesarean section. Dams were decapitated to obtain the fetuses by cesarean section, and fetuses were rapidly frozen in an acetone-dry ice mixture. Using rapid freezing and shaving methods, the calibers of the DA, pulmonary artery (PA) and descending aorta (Ao) were measured to evaluate the effects of treatment. L-NAME reduced the DA calibers to 86% of the initial values, but recovery to the control levels occurred 6 hr after the injection. Indomethacin decreased the DA calibers to 34% of the control values and sustained the DA constriction until 24 hr after the treatment. Methylene blue caused DA constriction to almost the same degree as indomethacin, but the levels normalized within 24 hr after the treatment. We conclude that L-NAME caused a slight constriction of the DA, whereas methylene blue and indomethacin caused marked constriction of the vessels, suggesting that the NO-cGMP system as well as prostaglandins contribute to the DA patency.
本研究的目的是探讨一氧化氮（NO）和环磷酸鸟苷（cGMP）系统在调节胎鼠动脉导管（DA）通畅中的作用。在剖宫产术前的不同时间，给怀孕大鼠腹腔注射NO合酶（NOS）抑制剂N(G)-硝基-L-精氨酸甲酯（L-NAME，50 mg/kg）、可溶性鸟苷酸环化酶抑制剂亚甲蓝（30、50和100 mg/kg）或环氧合酶抑制剂吲哚美辛（3 mg/kg，口服）。通过剖宫产术将母鼠断头以获取胎儿，然后将胎儿迅速置于丙酮-干冰混合物中冷冻。采用快速冷冻和切片方法，测量DA、肺动脉（PA）和降主动脉（Ao）的管径，以评估治疗效果。L-NAME使DA管径降至初始值的86%，但注射后6小时恢复至对照水平。吲哚美辛使DA管径降至对照值的34%，并使DA持续收缩至治疗后24小时。亚甲蓝引起的DA收缩程度与吲哚美辛几乎相同，但治疗后24小时内水平恢复正常。我们得出结论，L-NAME引起DA轻微收缩，而亚甲蓝和吲哚美辛引起血管明显收缩，这表明NO-cGMP系统以及前列腺素对DA的通畅有影响。
