Investigating The Correlation Between 5-hydroxytryptamine And Hypertensive Disorder Complicating Pregnancy

Hypertensive disorder complicating pregnancy is a major causeof perinatal morbidity and mortality. The etiopathogenisis ofHypertensive disorder complicating pregnancy is very multiplicity.The primary cause of preeclampsia is still unknown. Here westudied 5-hydroxytryptamine (serotonin) and its possiblemechanism involved in hypertensive disorder complicatingpregnancy.In 1960, Poulson et al. proposed 5-hydroxytryptamine as anetiological factor in preeclampsia. In 1963, Senior et al.demonstrated the presence of significantly raised levels of5-hydroxytryptamine in placentas of preeclamptic patientscompared to controls. The urinary excretion of5-hydroxytryptamine metabolites is also increased in preeclampsia.5-hydroxytryptamine is a naturally occurring vasoactivesubstance found in the brain, intestine, platelets and other tissue.5-hydroxytryptamine has complex and multiple biologic activity,involve in miscellaneous physiological effects of central nervoussystem, alimentary system, systema circulatorium andimmunologic system, also relate to various diseases.At domestic and abroad, the data of 5-hydroxytryptamine andits possible mechanism involved in hypertensive disordercomplicating pregnancy are mainly about such aspects :①Theconcentrations of 5-hydroxytryptamine: In the free circulatingplatelet derived 5-hydroxytryptamine, in the platelet-poor plasma,in the urinary excretion and in the umbilical core blood ofpreeclamptic pregnant women were found to be significantlyhigher than in the normal pregnant controls. ② Monoamineoxidase (MAO), which inactivates serotonin, is localized in thesyncytiotrophoblast and decidua. In placental tissue frompreeclamptic pregnancies, the activity of MAO is lower and5-hydroxytryptamine levels are higher than in placental tissue fromnormal pregnancies.③5-hydroxytryptamine may participate in themechanism of vascular resistance control in human placenta,feto-placental blood flow, and 5-hydroxytryptamine as one of themost active vasopressor substance of the human feto-placentalcirculation. 5-hydroxytryptamine has complex and multiplecardiovascular effects, which led to its designation as anamphibaric molecule to regulate maternal blood pressure.④Theeffects of 5-hydroxytryptamine on the secretary activity of humanplacenta. ⑤ Expression 5-hydroxytryptamine and5-hydroxytryptamine receptor(5-HTR) in the syncytiotrophoblast,cytotrophoblast and decidua.Placenta is the only channel for transport of nutrients to theconceptus and the fetal nutrient demands increase exponentially toterm. Placental unit plays an important role in the maintenance ofpregnancy, the growth of the fetus, and the timing of birth. Thispivotal role of the placenta is largely accountable to its ability toproduce a large variety of hormone, growth factors and cytokinesto act in paracrine and endocrine manners on both fetal andmaternal physiology throughout pregnancy.In the last few years, many people want to explore themechanism of immunization imbalance involved in hypertensivedisorder complicating pregnancy. There are various hormones,growth factors and cytokines produced by placenta take part in thedevelopment of hypertensive disorder complicating pregnancy.5-hydroxytryptamine can augment placental secretion effect, wewant to determine whether it throughout effect the placentalsecretion or other function to take part in the development ofhypertensive disorder complicating pregnancy.To determine whether levels of 5-hydroxytryptamine and5-hydroxyindoleacetic acid (5-HIAA) play an important role in thepathogenesis of hypertensive disorder complicating pregnancy, wemeasured maternal venous blood with hypertensive disordercomplicating pregnancy and normotensive pregnant women inthird trimester as control, and umbilical venous blood werecollected from newborns in each groups. Plasma5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels weremeasured by high performance liquid chromatography fluorometry.5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels inmaternal and umbilical blood of hypertensive disordercomplicating pregnancy groups were significantly higher than thatin the control group (P<0.01). The markedly elevated plasma5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels mightbe caused by the increased release of 5-hydroxytryptamine byplatelet. The result showed that elevated levels of5-hydroxytryptamine and 5-hydroxyindoleacetic acid in patientswith hypertensive disorder complicating pregnancy might take partin the pathogenesis of hypertensive disorder complicatingpregnancy.We investigate the effects of 5-hydroxytryptamine on apoptosisof cultured human cytotrophoblast cells and its possiblemechanism involved in hypertensive disorder complicatingpregnancy. Apoptosis rate was measured by TdT-mediatedbiotinyated-dUTP nick end labeling (TUNEL) and morphologicalfeatures of apoptosis cells were observed under electronmicroscope. Compared with the normal control group apoptosisindex, 5-hydroxytryptamine group was found significantly increaseof apoptosis index of cytotrophoblast cells .Every group'ssignificant morphologies of apoptotic cytotrophoblast cells werefound under the electronic microscope. Apoptotic cytotrophoblastcells were obviously compact and the chromatins were formed asmass and apoptotic bodies were observed under the electronicmicroscope. 5-hydroxytryptamine can promote the apoptosis ofhuman cytotrophoblast cells and which may be correlated with themechanism of hypertensive disorder complicating pregnancyL-type calcium channels are also expressed in cytotrophoblastcells where they regulate a multitude of processes includingsecretion of hormone and transmitters, gene expression, mRNAstability, cell differentiation, apoptosis and the activity of other ionchannels. The functional expression of calcium channels has beenscarcely studied in human placental cytotrophoblast cell. We havepresently sought to characterize L-type calcium channels and Ca2+currents of the cultured human placental cytotrophoblast cell bywhole cell patch-clamp recordings. The purpose of this work wasto explore, by electrophysiological methods, L-type calciumchannels in cytotrophoblast cells from human placenta.We provide the evidence for the characteristic of L-typecalcium channels of cytotrophoblast cell by patch-clamprecordings. The current-voltage relationship demonstrated thepotential dependency of this current, which activated from-10~0mV, reached a maximum at -30~-40mV and was totallyinactivated at +50~+60mV. This fast inactivating inward currentwas blocked either by Co2+ (20μM) or by nimodpine (10μM),which are special L-type calcium channels blocker.Tetrodotoxin(TTX,20μM), a specific blocker of Na+ channels andflunarizne(10μM), T-type calcium channels blocker, failed to affectthe voltage-dependent inward current. This channel activation wasby 5-hydroxytryptamine. 5-hydroxytryptamine (1μM, 10μM)could increase the Ca2+current and the maximal amplitude reachedat 100.51±9.70 (pA) and 109.00±10.63 (pA) respectively.(Compared with the maximal amplitude of primordial Ca2+current,P<0.05, P<0.01, respectively). The effects of 5-hydroxytryptamineincreasing the calcium current were significantly blocked by Co2+(20μM), which suggested that 5-hydroxytryptamine, may be anL-type calcium channels activating agent. Although the mechanisminvolved in this process was not explored, it could be possible thatthe 5-hydroxytryptamine receptor mediate the route of calciumentry being rich in cytotrophoblast cell.We also showed for the first time a result that5-hydroxytryptamine increased intracellular free calciumconcentration of culture human cytotrophoblast cells. Supervise thedynamic change of intracellular free calcium concentration ofcytotrophoblast cells under laser scanning confocal microscopy(LSCM) continuous scanning. we have found that after application5-hydroxytryptamine(10μmol·L-1) the intracellular free calciumwas increased significantly. Moreover, the effects of5-hydroxytryptamine were reduced either byNimodpine(10μmol · L-1) or byketanserin(10μmol·L-1).Pretreatment of cytotrophoblast cells withthe Ca2+ channel inhibitor and 5-hydroxytryptamine receptorblocker, Nimodpine and ketanserin, reduced the intracellular freecalcium concentration increase in cytotrophoblast cells. Althoughthe exact mechanism of that activation was beyond the scope of thepresent study, it appears that 5-hydroxytryptamine stimuli that canlead to sustained calcium entry and also can lead to L-type calciumchannels activity.All the results above suggest that 5-hydroxytryptamineinvolved in the processes of hypertensive disorder complicatingpregnancy. 5-hydroxytryptamine is an etiological factor and mayplay an important role in the pathological processes ofhypertensive disorder complicating pregnancy. The mechanismmay be complex and multiple, and unknown until now.