Ladipo C O, Elias S O, Oduwole B P, Ojelkere O, Ojobor P D, Sofola O A
Physiology, College of Medicine, University of Lagos, Idi-Araba, Lagos.
Nig Q J Hosp Med. 2007 Jan-Mar;17(1):13-7. doi: 10.4314/nqjhm.v17i1.12534.
Chloroquine (CQ) remains the household drug for the treatment of malaria especially among pregnant women. However, there are reports that CQ inhibits the contractile process in non-pregnant rat's uterus. The aim of this study is to compare responses to CQ between non-pregnant and pregnant mice and identify some mechanisms involved. Experiments were carried out in non-pregnant and pregnant mice pretreated 24 hours before with 1.5 mg/kg-body weight stilboesterol given orally. Strips of uterine smooth muscle, approximately 5 mm in diameter, were mounted in a 20 ml organ bath containing De Jalon solution bubbled with a 95% O2-5% CO2 gas mixture. Responses of the strips to graded concentration of acetylcholine (ACh) (10(-9) to 10(-5) mol/L), oxytocin (OXY) (10(-5) to 10(-2) IU/ml) and CQ (10(-6) to 4 x 10(-4) mol/L) were investigated. The strips were then incubated in 4 x 10(-4) mol/L CQ for 15 mins and the cumulative dose responses for OXY were repeated. To investigate mechanism of action, the strips were incubated for 15 mins in N(w)-nitro L-arginine methyl ester (L-NAME) and the cumulative responses to CQ repeated. Each investigation was carried out in fresh tissue mounted on Grass Model FT03 force transducer coupled unto a 4-channel Grass Model 7D Polygraph. CQ (low to moderate level), ACh and OXY led to increases in contractile responses in the uteri. There were greater contractile responses in non-pregnant than pregnant mice to CQ and ACh. At high doses, CQ had an inhibitory effect on the uterine contraction. Incubating in CQ led to abolition of contractile responses to OXY and ACh. In the presence of L-NAME, inhibitory effect of CQ at high doses was attenuated in pregnant mice only. The results suggest that CQ at high doses inhibits contractile responses in non-pregnant and pregnant mice. Enhanced nitric oxide bioactivity attenuated this inhibitory effect.
氯喹（CQ）仍然是治疗疟疾的常用药物，尤其是在孕妇中。然而，有报道称CQ会抑制未怀孕大鼠子宫的收缩过程。本研究的目的是比较未怀孕和怀孕小鼠对CQ的反应，并确定其中涉及的一些机制。实验在未怀孕和怀孕的小鼠中进行，这些小鼠在实验前24小时口服给予1.5mg/kg体重的己烯雌酚。将直径约5mm的子宫平滑肌条安装在含有用95%O₂-5%CO₂气体混合物鼓泡的德贾隆溶液的20ml器官浴中。研究了这些肌条对不同浓度乙酰胆碱（ACh）（10⁻⁹至10⁻⁵mol/L）、催产素（OXY）（10⁻⁵至10⁻²IU/ml）和CQ（10⁻⁶至4×10⁻⁴mol/L）的反应。然后将肌条在4×10⁻⁴mol/L的CQ中孵育15分钟，并重复对OXY的累积剂量反应。为了研究作用机制，将肌条在N⁰-硝基-L-精氨酸甲酯（L-NAME）中孵育15分钟，并重复对CQ的累积反应。每项研究都在安装在Grass Model FT03力传感器上并连接到4通道Grass Model 7D记录仪的新鲜组织中进行。CQ（低至中等水平）、ACh和OXY导致子宫收缩反应增加。未怀孕小鼠对CQ和ACh的收缩反应比怀孕小鼠更强。高剂量时，CQ对子宫收缩有抑制作用。在CQ中孵育导致对OXY和ACh的收缩反应消失。在L-NAME存在的情况下，高剂量CQ的抑制作用仅在怀孕小鼠中减弱。结果表明，高剂量的CQ抑制未怀孕和怀孕小鼠的收缩反应。一氧化氮生物活性增强减弱了这种抑制作用。
