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.
Biomarkers ; Bipolar Disorder ; Humans ; Mood Disorders ; Neurotransmitter Agents ; Urotensins

OBJECTIVETo 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.

METHODSA 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.

RESULTSAfter 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).

CONCLUSIONThe 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).

Acupuncture Points ; Acupuncture Therapy ; methods ; Humans ; Neuropeptide Y ; blood ; Spondylosis ; blood ; therapy ; Urotensins ; blood ; Vertebral Artery

OBJECTIVETo 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.

METHODSA 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.

RESULTSThere 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).

CONCLUSIONSCgA 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.

Cardiomyopathy, Dilated ; blood ; Child ; Child, Preschool ; Chromogranin A ; blood ; Chronic Disease ; Endocardial Fibroelastosis ; blood ; Female ; Heart Failure ; blood ; Humans ; Infant ; Male ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Urotensins ; blood ; Ventricular Function, Left

BACKGROUNDUrotensin 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.

METHODSGrowth-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.

RESULTSUII 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.

CONCLUSIONUII 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.

Adventitia ; cytology ; Animals ; Aorta ; cytology ; Cells, Cultured ; Chemokine CCL2 ; genetics ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Urotensins ; pharmacology

OBJECTIVETo 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.

METHODThirty 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.

RESULT(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).

CONCLUSIONThere 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.

Adolescent ; Blood Pressure ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; complications ; metabolism ; physiopathology ; Humans ; Hypertension, Pulmonary ; etiology ; metabolism ; physiopathology ; Immunohistochemistry ; In Situ Hybridization ; Infant ; Lung ; metabolism ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Severity of Illness Index ; Urotensins ; genetics ; metabolism

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.
Animals ; Blood Pressure ; drug effects ; Brain ; metabolism ; Hypertension ; physiopathology ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reactive Oxygen Species ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Superoxide Dismutase ; metabolism ; Urotensins ; pharmacology

OBJECTIVETo study the role of urotension-II in serum and bronchoalveolar lavage fluid (BALF) in the process of airway remodelling in asthmatic rats.

METHODSThirty-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.

RESULTSThe 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.

CONCLUSIONSThe 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.

Airway Remodeling ; Animals ; Asthma ; metabolism ; pathology ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Male ; Muscle, Smooth ; pathology ; Rats ; Rats, Sprague-Dawley ; Urotensins ; analysis ; blood

BACKGROUNDUrotensin 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.

METHODSAdventitial 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.

RESULTSUII 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.

CONCLUSIONThis 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.

Actins ; analysis ; genetics ; Animals ; Aorta ; cytology ; Cell Transdifferentiation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Fibroblasts ; cytology ; drug effects ; Male ; Myofibroblasts ; cytology ; Phenotype ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Signal Transduction ; Transforming Growth Factor beta1 ; physiology ; Urotensins ; antagonists & inhibitors ; pharmacology

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.
Animals ; Blood Glucose ; metabolism ; Cell Line ; Glucokinase ; metabolism ; Homeodomain Proteins ; metabolism ; Insulin ; secretion ; Insulin-Secreting Cells ; metabolism ; physiology ; secretion ; Male ; Mice ; Rats ; Rats, Wistar ; Trans-Activators ; metabolism ; Urotensins ; pharmacology

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Benzimidazoles ; therapeutic use ; Hypertension ; blood ; drug therapy ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; blood ; Random Allocation ; Rats ; Rats, Inbred SHR ; Tetrazoles ; therapeutic use ; Urotensins ; blood