Effect of the vascular endothelium on noradrenaline‐induced contractions in non‐pregnant and pregnant guinea‐pig uterine arteries
Effect of the vascular endothelium on noradrenaline‐induced contractions in non‐pregnant and pregnant guinea‐pig uterine arteries
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血管内皮对去甲肾上腺素诱导的非妊娠和妊娠豚鼠子宫动脉收缩的影响
DOI：
10.1111/j.1476-5381.1995.tb13276.x
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发表时间：
1995
影响因子：
7.3
通讯作者：
S. Jovanović
中科院分区：
文献类型：
--
作者：
A. Jovanovic;L. Grbović;S. Jovanović
1研究了妊娠对去甲肾上腺素介导的豚鼠子宫动脉环收缩的影响，包括完整和剥脱内皮。2去甲肾上腺素（25 nm − 100 μm）诱导非妊娠和妊娠豚鼠子宫动脉环的浓度依赖性收缩，内皮完整，pD 2和最大反应值相似（非妊娠：pD 2 = 5.85 ± 0.02，最大反应= 121 ± 8.2%;妊娠：pD 2 = 5.81 ± 0.04，最大反应= 122 ± 9.1%）。去除内皮不影响去甲肾上腺素诱导的非妊娠豚鼠子宫动脉收缩（pD 2 = 5.97 ± 0.02，最大反应= 119 ± 8.6%）。相比之下，在妊娠豚鼠动脉中，去除内皮使去甲肾上腺素的浓度-反应曲线向左移动，而不影响最大反应值（pD 2 = 6.36 ± 0.03，最大反应= 120 ± 9.0%）。3去甲肾上腺素的pKA值：未妊娠豚鼠子宫动脉（内皮完整和剥脱）分别为5.76 ± 0.09和5.82 ± 0.10，妊娠豚鼠子宫动脉（内皮完整和剥脱）分别为5.74 ± 0.09和5.72 ± 0.07。4除内皮剥脱的妊娠豚鼠子宫动脉外，所有类型血管的去甲肾上腺素受体占用-反应关系均为线性，因为获得的去甲肾上腺素半最大反应为44.8 ± 6.9%。（非妊娠豚鼠子宫动脉，内皮完整），43.3 ± 6.1%（内皮剥脱的非妊娠豚鼠子宫动脉）和44.3 ± 6.3%（内皮完整的妊娠豚鼠子宫动脉）受体占有率。在内皮剥脱的妊娠豚鼠子宫动脉中，去甲肾上腺素的占用-反应关系为非线性，因为获得的去甲肾上腺素半数最大反应为19.7 ± 3.3%受体占用。5 NG-单甲基-L-精氨酸（100 μm）和吲哚美辛（10 μm）不影响豚鼠子宫动脉中去甲肾上腺素的浓度-反应曲线，无论妊娠状态或内皮状况如何。[6]在静态制剂中，α肾上腺素受体拮抗剂哌唑嗪（5-50 nm）和育亨宾（1-10 μm）使去甲肾上腺素的曲线产生平行的α位移，Schild曲线的斜率与1无显著差异。限制为斜率为1的曲线给出了以下对数KB值：哌唑嗪与育亨宾：内皮完整的非妊娠豚鼠子宫动脉为8.78 ± 0.03 vs. 6.41 ± 0.02，内皮剥脱的非妊娠豚鼠子宫动脉为8.95 ± 0.03 vs. 6.34 ± 0.02，内皮完整的妊娠豚鼠子宫动脉为8.91 ± 0.01 vs. 6.44 ± 0.03，内皮剥脱的妊娠豚鼠子宫动脉为9.07 ± 0.01 vs. 6.52 ± 0.03。7可以得出结论，最初，非妊娠和妊娠豚鼠子宫动脉之间的去甲肾上腺素作用没有差异，但在去除内皮后，妊娠豚鼠子宫动脉对去甲肾上腺素更敏感，这与该组织中去甲肾上腺素受体储备增加有关。可能是内皮细胞的舒张因子介导了这种效应，但不太可能是一氧化氮或前列环素。拮抗剂亲和力和去甲肾上腺素本身的亲和力表明，α肾上腺素受体的相同亚型（可能是α1亚型）参与了去甲肾上腺素诱导的非妊娠和妊娠豚鼠子宫动脉（有或无内皮）收缩。
1 The effect of pregnancy on noradrenaline‐mediated contraction of guinea‐pig uterine artery rings with both intact and denuded endothelium was investigated. 2 Noradrenaline (25 nm − 100 μm) induced concentration‐dependent contraction of non‐pregnant and pregnant guinea‐pig uterine arterial rings with intact endothelium with similar pD2 and maximal response values (non‐pregnant: pD2 = 5.85 ± 0.02, maximal response = 121 ± 8.2%; pregnant: pD2 = 5.81 ± 0.04, maximal response = 122 ± 9.1%). Removal of endothelium did not affect noradrenaline‐induced contractions in non‐pregnant guinea‐pig uterine artery (pD2 = 5.97 ± 0.02, maximal response = 119 ± 8.6%). In contrast, in arteries from pregnant guinea‐pigs, removal of endothelium shifted concentration‐response curve for noradrenaline to the left, without affecting maximal response value (pD2 = 6.36 ± 0.03, maximal response = 120 ± 9.0%). 3 The pKA values for noradrenaline were: 5.76 ± 0.09 and 5.82 ± 0.10 for non‐pregnant guinea‐pig uterine artery with intact and denuded endothelium, respectively and 5.74 ± 0.09 and 5.72 ± 0.07 for pregnant guinea‐pig uterine artery with intact and denuded endothelium, respectively. 4 The receptor occupancy‐response relationship for noradrenaline was linear for all types of vessels, except for pregnant guinea‐pig uterine artery with denuded endothelium, since half‐maximal response to noradrenaline was obtained with 44.8 ± 6.9% (non‐pregnant guinea‐pig uterine artery with intact endothelium), 43.3 ± 6.1% (non‐pregnant guinea‐pig uterine artery with denuded endothelium) and 44.3 ± 6.3% (pregnant guinea‐pig uterine artery with intact endothelium) receptor occupancy. In pregnant guinea‐pig uterine artery with denuded endothelium, occupancy‐response relationship for noradrenaline was non‐linear since half‐maximal response to noradrenaline was obtained with 19.7 ± 3.3% receptor occupancy. 5 NG‐monomethyl‐l‐arginine (100 μm) and indomethacin (10 μm) did not affect concentration‐response curve for noradrenaline in guinea‐pig uterine arteries, regardless of pregnancy status or endothelial condition. 6 In quiescent preparations, the α‐adrenoceptor antagonists, prazosin (5–50 nm) and yohimbine (1–10 μm) produced parallel rightward shifts of the curves for noradrenaline and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following—log KB values: prazosin vs. yohimbine 8.78 ± 0.03 vs. 6.41 ± 0.02 for non‐pregnant guinea‐pig uterine artery with intact endothelium, 8.95 ± 0.03 vs. 6.34 ± 0.02 for non‐pregnant guinea‐pig uterine artery with denuded endothelium, 8.91 ± 0.01 vs. 6.44 ± 0.03 for pregnant guinea‐pig uterine artery with intact endothelium and 9.07 ± 0.01 vs. 6.52 ± 0.03 for pregnant guinea‐pig uterine artery with denuded endothelium. 7 It is concluded that initially there is no difference in noradrenaline action between uterine arteries from non‐pregnant and pregnant guinea‐pigs, but after removal of the endothelium the pregnant guinea‐pig uterine artery is more sensitive to noradrenaline, which is related to increased receptor reserve for noradrenaline in this tissue. It is probable that relaxing factor derived from the endothelium mediates this effect, but it is unlikely to be nitric oxide or prostacyclin. Antagonist affinities and affinity of noradrenaline itself suggests that an identical subtype of α‐adrenoceptor, probably the α1 subtype, is involved in the noradrenaline‐induced contraction of non‐pregnant and pregnant guinea‐pig uterine artery with or without endothelium.
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