Takizawa T, Horikoshi E, Kamata A
Department of Developmental Biotechnology, Azabu University School of Veterinary Medicine, Sagamihara, Japan.
Biol Neonate. 2000 Nov;78(4):300-3. doi: 10.1159/000014283.
We studied the combined effects of indomethacin, a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on the patency of the ductus arteriosus (DA) in fetal rats. Pregnant rats were administered indomethacin (3 mg/kg) orally 3 h before cesarean section, and then L-NAME (5 and 50 mg/kg), D-NAME, an enantiomer of L-NAME (50 mg/kg), or methylene blue, a soluble guanylate cyclase inhibitor (100 mg/kg), was injected intraperitoneally at various times before the cesarean section. Using rapid freezing and shaving methods, the calibers of the DA were measured. Compared with the indomethacin alone group, L-NAME caused a rapid and marked increase in the DA caliber 0.5 h after injection in fetal rats in which the DA was constricted by treatment with indomethacin. Subsequently, the transient ductal dilatation was completely reversed by 3 h after the L-NAME injection. Methylene blue also caused a biphasic response, but D-NAME did not affect the DA caliber. We conclude that the inhibition of both cyclooxygenase (indomethacin) and NO synthase (L-NAME) or NO action (methylene blue) causes a biphasic effect on the DA caliber in fetal rats.
我们研究了环氧化酶抑制剂吲哚美辛和一氧化氮（NO）合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）对胎鼠动脉导管（DA）通畅性的联合作用。剖宫产术前3小时给孕鼠口服吲哚美辛（3mg/kg），然后在剖宫产术前不同时间腹腔注射L-NAME（5和50mg/kg）、L-NAME的对映体D-NAME（50mg/kg）或可溶性鸟苷酸环化酶抑制剂亚甲蓝（100mg/kg）。采用快速冷冻和刮削法测量DA的管径。与单独使用吲哚美辛组相比，在经吲哚美辛处理使DA收缩的胎鼠中，L-NAME在注射后0.5小时使DA管径迅速且显著增加。随后，L-NAME注射后3小时，短暂的导管扩张完全逆转。亚甲蓝也引起双相反应，但D-NAME不影响DA管径。我们得出结论，环氧化酶（吲哚美辛）和NO合酶（L-NAME）或NO作用（亚甲蓝）的双重抑制对胎鼠DA管径产生双相效应。
