Weiner C P, Thompson L P, Liu K Z, Herrig J E
Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City 52242.
Am J Physiol. 1992 Dec;263(6 Pt 2):H1764-9. doi: 10.1152/ajpheart.1992.263.6.H1764.
Because platelet activation and serotonin have been implicated in preeclamptic hypertension, we investigated the effect of pregnancy on the contractile response to this agent. Prior studies have shown that the vascular contractions to norepinephrine, angiotensin II, and thromboxane are reduced during normal pregnancy by the altered release of endothelium-derived vasoactive substances. We hypothesized that the contraction to serotonin would also be reduced during pregnancy by an endothelium-dependent mechanism. Isolated ring segments from uterine and carotid arteries of near-term pregnant and nonpregnant guinea pigs were studied after stimulating a small amount of active tone with prostaglandin F2 alpha. Serotonin (10(-8) to 10(-5) M) contractile responses of both arteries were reduced by pregnancy. Regardless of pregnancy status, the contractile responses of the uterine artery to serotonin were severalfold greater than that of the carotid artery whose maximum averaged only 10% of the 120 mM KCl contraction. Denudation of uterine artery abolished acetylcholine-stimulated relaxation in vessels from pregnant and nonpregnant animals. However, serotonin-induced contractions were enhanced by denudation only in ring segments obtained from pregnant animals. Nitric oxide synthase inhibition by either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine and cyclooxygenase inhibition by indomethacin had no effect on serotonin-induced contraction of intact uterine artery regardless of pregnancy. L-NMMA modestly enhanced the intact carotid arterial response to 10(-5) M serotonin independent of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
由于血小板活化和血清素与子痫前期高血压有关,我们研究了妊娠对血管对该物质收缩反应的影响。先前的研究表明,在正常妊娠期间,由于内皮源性血管活性物质释放的改变,去甲肾上腺素、血管紧张素II和血栓素引起的血管收缩会减弱。我们假设,在妊娠期间,血清素引起的收缩也会通过内皮依赖性机制而减弱。在用前列腺素F2α刺激产生少量主动张力后,对近足月妊娠和未妊娠豚鼠的子宫和颈动脉的离体环段进行了研究。妊娠使两条动脉对血清素(10^(-8)至10^(-5)M)的收缩反应均减弱。无论妊娠状态如何,子宫动脉对血清素的收缩反应都比颈动脉大几倍,颈动脉的最大收缩反应平均仅为120mM氯化钾收缩反应的10%。去除子宫动脉内皮可消除乙酰胆碱刺激的妊娠和未妊娠动物血管的舒张。然而,血清素诱导的收缩仅在取自妊娠动物的环段中因去除内皮而增强。无论妊娠与否,NG-单甲基-L-精氨酸(L-NMMA)或Nω-硝基-L-精氨酸抑制一氧化氮合酶以及吲哚美辛抑制环氧化酶对完整子宫动脉的血清素诱导收缩均无影响。L-NMMA适度增强了完整颈动脉对10^(-5)M血清素的反应,与妊娠无关。(摘要截短于250字)