title: Progesterone suppressed vasoconstriction in human umbilical vein via reducing calcium entry.
abstract: The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists. Further testing showed that progesterone and nifedipine (a blocker for L-type calcium channels) produced similar inhibitory effects on PE-, 5-HT-, Bay-k8644-, KCl-induced vasoconstriction in Krebs solution as well as CaCl2-induced vasoconstriction in Ca(2+)-free Krebs solution. But the inhibitory effect of mibefradil (mibe, a blocker for L-type (CaV1.2) and T-type calcium channels (CaV3.2)) on PE-, 5-HT-induced vasoconstriction was significantly greater than progesterone or nifedipine in Krebs solution. Furthermore, progesterone did not affect the vasoconstriction caused by PE, 5-HT, or caffeine in Ca(2+)-free Krebs solution. In addition, incubation HUV with progesterone did not change CaV1.2 and progesterone receptor (PR) expressions. The results gained demonstrated that progesterone could suppress multiple agonist-induced vasoconstrictions in HUV, mainly due to a reduction of calcium entry through L-type calcium channels, not endothelium-dependent vascular relaxation pathways, potassium channels, or Ca(2+) release from intracellular stores, providing new information important to further understanding the contribution of progesterone in the regulation of the placental-fetal circulation.
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Tao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China; Center for Perinatal Biology, Loma Linda University, CA, USA. Electronic address: xuzhice@suda.edu.cn.
authors.forename: Zhice
authors.initials: Z
authors.lastname: Xu
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011375:Progesterone Reductase / Q000235:genetics; D012701:Serotonin / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D026902:Potassium Channel Blockers; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D012701:Serotonin; D011374:Progesterone; D011375:Progesterone Reductase; D002118:Calcium; D007213:Indomethacin
keywords: Calcium entry; Human umbilical vein; Progesterone; Vasoconstriction