Jovanovic S, Grbovic L, Jovanovic A
Tayside Institute of Child Health, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY, Scotland, UK.
Mol Hum Reprod. 2000 Apr;6(4):361-8. doi: 10.1093/molehr/6.4.361.
In order to provide sufficient nutrients for fetal development, pregnancy is associated with a significant increase in uterine blood flow. Although vasoactive intestinal polypeptide (VIP) is considered to be an important regulator of uterine blood flow it is not known whether endothelium-derived relaxing factors contribute to VIP action in the uterine artery, whether pregnancy alters the effect of VIP in the uterine artery and/or whether VIP interacts with noradrenaline and acetylcholine on the uterine artery and whether pregnancy regulates this possible interaction. In the present study, VIP induced a concentration-dependent relaxation of guinea pig uterine arterial rings, both intact and denuded of endothelium. Pregnancy did not alter the relaxation of uterine artery in response to VIP. In all preparations, addition of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin and diethylcarbamazine did not modify the effect of VIP in uterine arteries. The VIP-receptor complex dissociation constant did not differ significantly between studied vessels, and in all experimental groups the relationship between receptor occupancy and the response was linear, with the receptor reserve (K(A)/EC(50)) close to unity. VIP did not modulate acetylcholine-induced relaxation or noradrenaline-induced contraction in both non-pregnant and pregnant guinea pig uterine arteries. This study has shown that: (i) VIP induces relaxation of guinea pig uterine artery acting as a partial agonist on receptors localized in smooth muscle; (ii) pregnancy does not alter the response of guinea pig uterine arteries to VIP and does not change the receptor affinity for VIP, the efficiency of the receptor coupling or the VIP receptor density; and (iii) VIP does not modulate effects of neurotransmitters on guinea pig uterine arteries and pregnancy is not associated with the changes of VIP-neurotransmitter interaction.
为了给胎儿发育提供充足的营养物质，孕期子宫血流量会显著增加。尽管血管活性肠肽（VIP）被认为是子宫血流量的重要调节因子，但尚不清楚内皮源性舒张因子是否参与VIP在子宫动脉中的作用，孕期是否会改变VIP在子宫动脉中的效应，和/或VIP是否与去甲肾上腺素及乙酰胆碱在子宫动脉上相互作用，以及孕期是否调节这种可能的相互作用。在本研究中，VIP可引起完整及去内皮的豚鼠子宫动脉环浓度依赖性舒张。孕期并未改变子宫动脉对VIP的舒张反应。在所有标本中，加入N(G)-单甲基-L-精氨酸（L-NMMA）、吲哚美辛和乙胺嗪均未改变VIP在子宫动脉中的效应。VIP受体复合物解离常数在各研究血管间无显著差异，且在所有实验组中，受体占有率与反应之间呈线性关系，受体储备（K(A)/EC(50)）接近1。在未孕和孕豚鼠子宫动脉中，VIP均未调节乙酰胆碱诱导的舒张或去甲肾上腺素诱导的收缩。本研究表明：（i）VIP通过作用于平滑肌中的受体作为部分激动剂诱导豚鼠子宫动脉舒张；（ii）孕期不改变豚鼠子宫动脉对VIP的反应，不改变受体对VIP的亲和力、受体偶联效率或VIP受体密度；（iii）VIP不调节神经递质对豚鼠子宫动脉的作用，且孕期与VIP-神经递质相互作用的改变无关。
