Role of urotensin-ii in saphenous vein graft disease

Abstract Objective: To elucidate the effect of diabetes mellitus (DM) on the atherosclerotic process in saphenous vein grafts by determining urotensin-II (U-II) levels in harvested saphenous veins of patients who underwent coronary artery bypass grafting (CABG). Methods: Coronary artery disease (CAD) patients who underwent CABG were divided into two groups: Group I (eight non-diabetic patients; CAD group) and Group II (13 patients; DM+CAD group). All patients underwent coronary angiography prior to surgery and Gensini score was used to determine the severity of coronary atherosclerosis. Saphenous vein samples were stained with hematoxylin-eosin and U-II, then damage score, H-Score, and vein layer thicknesses were calculated and statistically evaluated. Results: In light microscopic evaluation, significant difference was observed between the groups in terms of endothelial cells damage, internal elastic lamina degradation, and tunica media vascular smooth muscle cells (VSMCs) damage (P<0.001). U-II immunoreactivity was increased in tunica adventitia in the DM+CAD group (P=0.002). The increase in foam cells was directly proportional to the thickening of the subendothelial layer, and this increased U-II immunoreactivity. Gensini score was higher in the DM+CAD group than in the CAD group (P=0.002). Conclusion: Our results show that saphenous vein grafts are already atherosclerotic before they are grafted in CAD patients. This disease is more severe in diabetic CAD patients and these changes can be detected using U-II immunoreactivity.

Evaluation of Endothelial Dysfunction in Bipolar Affective Disorders: Serum Endocan and Urotensin-II Levels

OBJECTIVE: This study investigated changes in urotensin-II (U-II) and endocan levels which can be used as an early biological marker of endothelial injury in the episode and remission phases of bipolar affective disorder (BAD). METHODS: We compared endocan and U-II levels, which has been shown to be closely associated with neurotransmitter systems in addition to continuity of endothelial structure and inflammatory response, in patients with BAD in remission for at least one year (n=42) and in patients still in manic or depressive episodes (n=16) with healthy controls (n=30). RESULTS: Both endocan and U-II levels were significantly higher in the bipolar patients than in the controls. Endocan and U-II levels were also significantly correlated with one another (p=0.000, r=0.833). Both endocan (p=0.000) and U-II levels (p=0.000) were significantly higher in the bipolar attack group compared to the subjects in remission, and in the remission group compared to the controls. CONCLUSION: In this study we determined significantly higher endocan and U-II levels in BAD compared to the controls, while serum endocan and U-II levels of patients undergoing attacks were also significantly higher than those of the controls and also those of patients in remission.

Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9) / 中国针灸

<p><b>OBJECTIVE</b>To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients.</p><p><b>METHODS</b>A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups.</p><p><b>RESULTS</b>After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all <0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all <0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all <0.01). After treatment, ESCV scores were all increased remarkably in every group (all <0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (<0.05, <0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all <0.01) and the differences were significant among the groups (all <0.01).</p><p><b>CONCLUSION</b>The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).</p>

Changes in serum chromogranin A and urotensin II levels in children with chronic heart failure / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance.</p><p><b>METHODS</b>A total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis.</p><p><b>RESULTS</b>There were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05).</p><p><b>CONCLUSIONS</b>CgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.</p>

Urotensin II promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Urotensin II (UII), a potent vasoconstrictive peptide, is able to stimulate phenotypic differentiation of adventitial fibroblasts. This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 (MCP-1) expression in rat aortic adventitial fibroblasts, so as to explore possible mechanisms in the development of vascular inflammation.</p><p><b>METHODS</b>Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII (10(-10)-10(-7) mol/L) and inhibitors of signal transduction pathways for 1 to 24 hours. MCP-1 mRNA and protein expression and secretion were determined by RT-PCR, Western blotting analysis and enzyme-linked immunosorbent assay (ELISA), respectively.</p><p><b>RESULTS</b>UII dose- and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells, with maximal effect at 10(-8) mol/L at 3 hours for mRNA expression, 24 hours for protein expression in the cells, and 12 hours for protein secretion from the cells. Furthermore, the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411, Rho kinase inhibitor Y27632, protein kinase C (PKC) inhibitor H7, mitogen-activated protein kinase inhibitor PD98059, calcineurin inhibitor cyclosporine A, and the Ca(2+)channel blocker nicardipine.</p><p><b>CONCLUSION</b>UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase, PKC, mitogen-activated protein kinase, calcineurin and Ca(2+) channel signal transduction, thus contributing to adventitial inflammation.</p>

Expression and role of urotensin II on the lung of patients with pulmonary hypertension with congenital heart disease / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the expression of urotensin II (UII) on the lung of patients with pulmonary hypertension (PH) with congenital heart disease and investigate the meaning of this phenomenon.</p><p><b>METHOD</b>Thirty eight patients with CHD were divided into three groups according to pulmonary arterial systolic pressure (PASP) measured in cardiac catheterization and surgery: normal pulmonary pressure group (N group, PASP < 30 mm Hg, n = 10), mild PH group (M group, PASP ≥ 30 mm Hg, n = 15), severe or moderate PH group (S group, PASP ≥ 50 mm Hg, n = 13). The expression of UII protein and UII mRNA in pulmonary arterioles were measured separately by immunohistochemical (IHC) analysis and in situ hybridization (ISH) analysis.</p><p><b>RESULT</b>(1) The results of UIIIHC staining: The UII protein expression of group M was higher than that of group N (20.22 ± 3.58 vs. 14.34 ± 2.18, P < 0.01), but less than group S (20.22 ± 3.58 vs. 28.92 ± 3.22, P < 0.05). (2) The results of UIIISH mRNA staining were similar to IHC staining, the A value of group M was higher than group N (12.51 ± 2.02 vs. 8.85 ± 1.41, P < 0.05), less than that of group S(12.51 ± 2.02 vs. 25.35 ± 4.33, P < 0.01). (3) Correlation study: there was a positive correlation between the A values of UIIIHC and pulmonary hypertension (r = 0.64, P < 0.01, n = 38), a positive correlation between the A values of UIIISH and pulmonary hypertension (r = 0.58, P < 0.01, n = 38).</p><p><b>CONCLUSION</b>There was the expression of Urotensin II protein and mRNA in the lung of pulmonary hypertension patients with congenital heart disease, and these expression may involve the formation of pulmonary hypertension of congenital heart disease.</p>

Central reactive oxygen species mediate cardiovascular effects of urotensin II in spontaneously hypertensive rats / 生理学报

Central urotensin II (UII) may participate in the regulation of cardiovascular functions by stimulating sympathy pathway. However, the central mechanism remained unknown. Recent studies have shown that brain reactive oxygen species (ROS) mediate the sympatho-excitatory effects. In the present study, we tested the hypothesis that ROS mediate central cardiovascular effects of UII. Experiments were conducted in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Immunocytochemistry, intracerebroventricular (icv) infusion and lucigenin-enhanced chemiluminescence assay were employed to detect UII receptor expression and ROS level, respectively. The following results were obtained: (1) Expressions of UII receptors of rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) were increased in SHR rats compared with WKY rats (P < 0.05). (2) UII (icv) significantly increased mean arterial pressure (MAP) (P < 0.05), and the effect of UII was significantly more pronounced in SHR rats than that in WKY rats (P < 0.05); (3) Tempol (a superoxide dismutase mimic) or Urantide (an antagonist of UII receptor) pretreatments eliminated the pressor effect of UII (P < 0.05) in SHR rats; (4) Brain superoxide level was increased in UII-treated SHR rats compared with that in cerebrospinal fluid (CSF)-treated SHR rats (P < 0.05). These results indicate that ROS mediate central cardiovascular effects of UII in SHR rats and provide evidence for a novel relationship between UII and ROS.

Urotensin II inhibits glucokinase expression and glucose-induced insulin secretion / 生理学报

The purpose of the present study is to investigate the effects of urotensin II (UII) on insulin secretion in islet beta cells and the underlying mechanism. Glucose tolerance test was performed in Wistar rats to evaluate the effect of UII on the levels of plasma glucose and insulin. Static incubation experiment was employed to investigate the effect of UII on glucose-induced insulin secretion (GIIS) in betaTC-6 cells. After the incubation, insulin content and mRNA level in betaTC-6 cells were analyzed. Finally, Western blot was used to find out if UII could change the expression levels of pancreatic duodenal homeobox-1 (PDX-1) and glucokinase (GCK). It was observed that intravenous administration of UII (30, 300 nmol/kg) resulted in a significant decrease in insulin level 15 min after glucose load, and induced an obvious increase in plasma glucose 90 min after the load. In vitro, two hours of UII incubation inhibited GIIS in betaTC-6 cells without affecting insulin content and mRNA levels. The inhibitory effect of UII was blocked by UII receptor antagonist (urantide), and partially blunted by protein kinase C (PKC) inhibitor (chelerythrine) and somatostatin receptor antagonist (cyclosomatostatin). Moreover, we found that GCK protein level was significantly reduced by UII, while PDX-1, a key regulator of insulin gene transcription in beta cells, was not affected. These results suggest that UII-induced inhibition of GIIS in betaTC-6 cells are mediated by UII receptor and PKC pathway, as well as somatostatin receptor which could be activated by high dose of UII. The inhibitory effect of UII on insulin secretion is rather associated with a suppression of GCK expression than a regulation on PDX-1 expression.

Transforming growth factor-β1 involved in urotensin II-induced phenotypic differentiation of adventitial fibroblasts from rat aorta / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Urotensin II (UII) is a new vasoconstrictive peptide that may activate the adventitial fibroblasts. Transforming growth factor-β1 (TGF-β1) is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-β1 is involved in UII-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.</p><p><b>METHODS</b>Adventitial fibroblasts were prepared by the explant culture method. TGF-β1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of α-smooth nuscle actin (α-SM-actin), the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR (real-time RT-PCR) and Western blotting, respectively.</p><p><b>RESULTS</b>UII stimulated the secretion of TGF-β1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% (P < 0.01), than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10(-8) mol/L of UII (P < 0.01), which was increased by 59.9%, compared with in the control group (P < 0.01). The secretion of TGF-β1 induced by UII was significantly blocked by SB-710411 (10(-7) mol/L), a specific antagonist of UII receptor. In addition, both UII (10(-8) mol/L) and TGF-β1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UII was inhibited by the specific neutralizing antibody (20 µg/ml) of TGF-β1, while the α-SM-actin expression stimulated by TGF-β1 (20 ng/ml) was inhibited by SB-710411 (10(-7) mol/L), the UII receptor antagonist.</p><p><b>CONCLUSION</b>This study suggests that UII could induce TGF-β1 secretion in adventitial fibroblasts via UT activation, and TGF-β1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UII, and TGF-β1 signaling might be one of the important pathways by which UII is involved in vascular fibrosis.</p>

Changes in urotensin-II expression in airway remodelling in asthmatic rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the role of urotension-II in serum and bronchoalveolar lavage fluid (BALF) in the process of airway remodelling in asthmatic rats.</p><p><b>METHODS</b>Thirty-two male Sprague-Dawley (SD) rats were randomly divided into normal control and 2-week, 4-week and 8-week asthmatic groups (OVA inhalation of 2, 4 and 8 weeks respectively). Rats were sensitized and challenged by OVA to establish a model of asthma. The bronchial wall thickness and the airway smooth muscle thickness were measured by image analysis system. The urotension-II contents in serum and BALF were determined using ELISA.</p><p><b>RESULTS</b>The bronchial wall thickness and the airway smooth muscle thickness in the three asthmatic groups significantly increased compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the three asthmatic groups also increased significantly compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the 8-week asthmatic group were the highest, followed by the 4-week and the 2-week asthmatic groups (P<0.01). BALF urotension-II contents were positively correlated with the bronchial wall thickness and the airway smooth muscle thickness as well as serum U-II contents in the four groups.</p><p><b>CONCLUSIONS</b>The urotension-II contents in serum and BALF in the process of airway remodeling increase in asthmatic rats. The changes in serum and BALF urotension-II contents may be associated with airway remodeling in asthmatic rats.</p>

Protective effect of urantide against myocardial ischemia injury / 药学学报

This study is to investigate the protective effect of urantide against myocardial ischemia injury in mice and its mechanism. The ischemic model was made by using subcutaneous injection of isoproterenol (Iso) in mice, the change of ST segment of electrocardiogram (ECG) was observed, and the activitise of lactate dehydrogenase (LDH) and nitric oxide synthetase (NOS), the contents of malonaldehyde (MDA) and nitric oxide (NO) in serum were measured. The histopathological changes of myocardium were observed by using HE staining. The anoxia/reoxygenation (A/R) model of myocardial cells on neonatal Sprague-Dawley rats was established. Methyl thiazolyl tetrazolium (MTT) assay and confocal microscopy were respectively used to measure the viability and intracellular Ca2+ concentration in myocardial cells exposed to A/R. LDH activity and cTnI content in the cell culture medium were assayed for the evaluation of myocardial cells injury. The results revealed that urantide in the range of 3 - 30 microg kg(-1) iv markedly inhibited Iso-induced raise of the ST segment of ECG; 10 and 30 microg kg(-1) significantly reduced the increases of MDA content and LDH activity in mice serum, remarkably raised the activity of NOS and the content of NO. Urantide (10 and 30 microg kg(-1)) also significantly ameliorated myocardial ischemic injury. On the A/R model of myocardial cells, urantide (1 x 10(-6) - 1 x 10(-9) mol L(-1)) could evidently inhibit the increases of cTnI content, reduce the rise of intracellular Ca2+ concentration. Urantide (1 x 10(-6) - 1 x 10(-7)) mol L(-1) increased the viability of myocardial cells injured by A/R and cut down LDH activity in the cell culture medium. Therefore urantide has significant protective effect against myocardial ischemia or A/R injury via the inhibition of Ca2+ overload and the augmentation of NO synthesis.

Urotensina II en niños con enfermedades renales: nuevos aportes sobre un antiguo péptido / Urotensin-II in children with renal diseases: New messages from an ancient peptide

Human urotensin-II (hU-II) is one of the most potent vasoconstrictors in mammals, even more potent than endothelin. It has a wide range of vasoactive properties dependent on the anatomic site and the species studied. Although it is expressed mainly in the brain and spinal cord, it is also detected in other tissues, such as the kidney. It has been recognized for over 30 years, however only recently it has become a major focus of clinical researches. It has been suggested that U-II may have a possible autocrine/paracrine functions in kidney, and may be an important target molecule in studying renal pathophsiology. Previously, we investigated the level of U-II in children with minimal change nephrotic syndrome (MCNS), and to our knowledge there is no study about the possible role of U-II in other childhood glomerulonephritis. We firstly determined the expression of h U-II in kidneys of children with several glomerular diseases. In the lights of literature and our findings, this review describes mainly the possible role of U-II in children with renal diseases and summarizes what is known, and what must be known about the U-II

La urotensina II (U-II) humana es uno de los vasoconstrictores más fuertes en los mamíferos, es incluso más potente que la endotelina. Tiene un amplio espectro de propiedades vasoactivas según su localización anatómica y las especies estudiadas. Si bien se expresa fundamentalmente en el cerebro y en la médula espinal, también se la detecta en otros tejidos como el riñón. Aunque se la conoce desde hace más de 30 años, sólo recientemente se transformó en un objetivo principal de las investigaciones clínicas. Se sugirió que la U-II podría tener funciones autocrinas/paracrinas en el riñón y que podría ser una importante molécula blanco en el estudio de la fisiopatología renal. Con anterioridad investigamos el nivel de U-II en niños con síndrome nefrótico de cambios mínimos (SNCM) y según nuestro conocimiento no existe ningún estudio acerca del posible papel de la U-II en otras glomerulonefritis infantiles. En primer lugar determinamos la expresión de la U-II en riñones de niños con varias enfermedades glomerulares. En función de la literatura y de nuestros hallazgos, en esta revisión se describe esencialmente el posible papel de la U-II en niños con enfermedades renales y se resumen los conocimientos disponibles y lo que resta saber acerca de la U-II.

Relationship between polymorphism of urotensin II gene and type 2 diabetes in pedigrees / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between a polymorphism (rs228648) of urotensin II (UT-II) gene and type 2 diabetes in pedigrees.</p><p><b>METHODS</b>Patients and controls with/without familial history were enrolled in the same place.</p><p><b>RESULTS</b>Carriers with AG or AA genotype from pedigrees had higher disease risk than those with GG genotype (OR=1.98, 95% CI:1.19-3.29,OR=2.46,95% CI:1.39-4.34), the frequency of A allele was higher in the patients from pedigrees than inner controls and patients who had no familial history (P=0.01). The frequency of A allele was higher in the inner controls than outer ones (P=0.001). The insulin resistance index, insulin sensitivity index and pancreatic secretion index of inner controls with AG genotype were higher than those with GG genotype (All P < 0.05).</p><p><b>CONCLUSION</b>This polymorphism of UT-II gene might be a risk to type 2 diabetes, the insulin function of people from pedigrees is associated with the mutation.</p>

Effect of urotensin II on iNOS expression in human umbilical vein endothelial cells / 中国应用生理学杂志

<p><b>AIM</b>To observe the direct effect of urotensin II (U II) on the release of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) mRNA in human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>HUVEC were cultured with different concentrations of U II (10(-9)-10(-7) mol/L) for 24 hours. Then the supernatant was collected to detect the level of NO and the activity of iNOS, the expression of iNOS mRNA of HUVEC was measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>In comparison with controls, the level of NO, the activity of iNOS and the iNOS mRNA expression increased significantly (P < 0.05).</p><p><b>CONCLUSION</b>U II may up-regulate the expression of iNOS mRNA and increase NO generation in HUVEC, it suggests that U II may relax blood vessel by activating iNOS/NO pathway.</p>

Expression of Urotensin II and its receptor on right ventricle in rats of pulmonary hypertension / 中国应用生理学杂志

<p><b>AIM</b>To observe the expression of Urotensin II (U II) and its receptor (UT) on right ventricle in rats with chronic pulmonary hypertension induced by hypoxia and hypercapnia.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and hypoxia-hypercapnia 4-week group(HH). Mean pulmonary arterial pressure(MPAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+ S) were calculated separately. U II in plasma was measured using radioimmunoassay. The expression of U II was observed in right ventricle myocytes and right ventricle arteries by immunohistochemistry. The expression of U II mRNA and UT mRNA were observed in right ventricle myocytes and right ventricle arteries by in situ hybridization.</p><p><b>RESULTS</b>(1) The MPAP and RV/LV + S of HH group were higher respectively than those of NC group (P < 0.01, respectively). (2) The plasma U II content of HH group did not increased obviously than that of NC group. (3) The expression score of U II, U II mRNA, UT mRNA by right ventricle myocytes in HH group were higher significantly than those of NC group (P < 0.01 respectively). (4) The average value of integral light density (LD) of U II, U II mRNA, UT mRNA by right cardial arteries in HH group were higher significantly than those of NC group (P < 0.01, respectively).</p><p><b>CONCLUSION</b>The expression of U II in right ventricle arteries and right ventricle myocytes increase significantly during the formation of pulmonary hypertension and right ventricle hypertrophy in rats chronically exposed to hypoxia-hypercapnia. These changes indicate that U II might be involved in right ventricle remodeling, which promotes proliferation of cardiac muscle cells.</p>

Effect of urotensin II on proliferative potential and phosphorylation of extracellular signal-regulated kinase 1/2 of adventitial fibroblasts from spontaneously hypertensive rat / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of urotensin II ( U II ) on the proliferative potential of adventitial fibroblasts (AFs) from spontaneously hypertensive rat (SHR) and to determine whether extracellular signal-regulated kinase 1/2 (ERK1/2) pathway is involved in this progress.</p><p><b>METHODS</b>3H-thymidine incorporation test was used to estimate the U II -induced proliferative potential of AFs from SHR and the influence of Urantide (U II receptor antagonist) and PD98059 (ERK1/2 inhibitor). Western blotting was used to test the U II -induced ERK1/2 phosphorylation as well as the effect of Urantide and PD98059 on U II -induced ERKl/2 phosphorylation.</p><p><b>RESULTS</b>U 11 increased the proliferative potential of AFs from SHR in a dose-dependent way. Urantide and PD98059 wholly or partly inhibited U II -induced proliferation of SHR-AFs. In SHR-AFs, U II induced the phosphorylation of ERK1/2 in a time-dependent way, which was completely inhibited by Urantide and PD98059.</p><p><b>CONCLUSION</b>U II can increase the proliferative potential of AFs from SHR and ERK1/2 pathway is partly involved in this progress.</p>

Effect of urotensin II on secretion of adrenomedullin from human vascular endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study the effect of human urotensin II (HU II) on secretion of adrenomedullin (ADM) from human vascular endothelial cells (HVEC) and its mechanism.</p><p><b>METHODS</b>In cultured HVEC, different concentrations of HUII were used to stimulate the ADM secretion from HVEC, and the inhibitors of different signal transduction pathway were used to investigate their effects on ADM secretion. The contents of ADM in medium were determined by radio immunoassay.</p><p><b>RESULTS</b>HUII stimulated secretion of ADM from HVEC in a time-dependent and concentration-dependent manner. The contents of ADM in the experiment groups were changed compared with that in control group (P < 0.05). The increase of ADM could be inhibited by inhibitor of extracellular signal-regulated protein kinase (PD(98059)), inhibitor of P38 kinase (SB(202190)), inhibitor of calmodulin (W(7)) and inhibitor of Ca(2+) (nicardipine) (P < 0.05). The inhibition ratio in those groups was 68%, 78%, 24% and 25% respectively. But the inhibitor of Calcineurin (CaN) and inhibitor of protein kinase C (H(7)) had no influence on the secretion of ADM from HVEC (P > 0.05).</p><p><b>CONCLUSION</b>The stimulated effect of HUII on the ADM secretion from HVEC may be mediated by Ca(2+), ERKs, CaM-PK and P38 signal transduction pathways.</p>

Expression of urotensin II and G-protein coupled receptor 14 mRNA in human pheochromocytoma tissues / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of urotensin II (U II) and G-protein coupled receptor 14 (GPR14) mRNA in human pheochromocytoma tissues.</p><p><b>METHODS</b>Total RNA from normal adrenal and pheochromocytoma tissues was extracted. The reverse transcription-polymerase chain reaction method was used to evaluate the levels of U II and GPR14 mRNA expression in human pheochromocytoma tissues.</p><p><b>RESULTS</b>There was no significant difference of U II and GPR14 mRNA expression between normal adrenal cortex and medulla. The expression of U II and GPR14 mRNA in pheochromocytoma was significantly lower than that in normal adrenal cortex and medulla (P < 0.05). The expression of GPR14 mRNA in adrenal pheochromocytomas was significantly lower than that of extra-adrenal pheochromocytomas (P < 0.05).</p><p><b>CONCLUSION</b>U II and GPR14 may play a role in the pathogenesis and hypertension regulating of pheochromocytoma.</p>

A vasoactive peptide: urotensin II / 中国医学科学院学报

Urotensin II (U II ) is currently the most potent vasoconstrictor. G-protein coupled receptor 14 ( GPR-14) is its specific receptor. This review mainly discribes the structure and distribution of U II and GPR14, the activities that U II and GPR14 stimulates proliferation of vascular smooth muscle cells and vasoconstriction, as well as its mechanism.

The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin II / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human urotensin II (UII) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UII is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UII mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UII.</p><p><b>METHODS</b>In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UII were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UII was measured using Fura-2/AM.</p><p><b>RESULTS</b>UII 10(-7) mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P < 0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P < 0.01). It promoted the cytosolic free calcium concentration increase of 18% (P < 0.01). CsA 10(-6) mol/L and H7 50 micromol/L inhibited UII-stimulated CaN activity by 45% (P < 0.01) and 21% (P < 0.05), respectively, while PD98059 50 micromol/L had no effect on CaN activity (P > 0.05). CsA 10(-6) mol/L inhibited UII-stimulated PKC activity by 14% (P < 0.05), while having no effect on MAPK activity (P > 0.05).</p><p><b>CONCLUSIONS</b>UII increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.</p>