Aim To investigate the effect of urotensin Ⅱ on vascular calcification.Methods Calcified VSMCs of rat in vitro were induced by β-glycerophosphate.Cellular calcium content,ALP activities,~(45)Ca accumulation and osteocalcin content were measured.Results Compared with those of control group,calcium content,ALP activities,~(45)Ca uptake and osteocalcin in calcified VSMCs increased greatly(P<0.01).Calcium content,ALP activities,~(45)Ca uptake and osteocalcin of calcified VSMCs stimulated by urotensin Ⅱ (10~(-10)、10~(-9) and 10~(-8) mol·L~(-1))were greatly increased in a concentration-dependent manner as compared with those of calcified group(P<0.01).Conclusion UrotensinⅡ aggravates the calcification of VSMCs induced by β-glycerophosphate.

Objective To investigate the role of endogenous Hydrogen Sulfide (H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking.Methods Male SD rats were randomly divided into a control group (breathing fresh air) and a passive smoking group [cigarette smoking (CS) passively] ,with 18 rats in each group.Six rats in each group were randomly intraporitoneally injected with normal saline, sodium hydrosulfide (NailS) or propargylglycine (PPG, an irreversible inhibitor of cystathionine-γ-lyase).The animals were divided into six subgroups,ie.Con group, Naris group, and PPG group, CS group, CS + Naris group, and CS + PPG group.After 4 months,lung histological change and airway tension were measured.The H2 S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay.The expression of cystathionine-γ-lyase (CSE) was measured by western blot.Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group(P < 0.05) ; the H2S levels of plasma were significantly higher in GS group,NariS group and CS + Naris group,and much lower in PPG group (P < 0.05, respectively).Compared with CS group, the H2 S levels of plasma were significantly higher in CS + Naris group, and much lower in CS + PPG group (P < 0.05, respectively).The H2S level of lung tissue in each group had no significant difference (P > 0.05).Compared with Con group, score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to Ach and KCI was significant augmented in CS group.Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS + NariS group(P < 0.05), and vise versa in CS + PPG group (P < 0.01).Conclusion H2 S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airway inflammation and airway responsiveness.

Objective:To discuss the variation of parameters in ambulatory blood pressure for neurally mediated syncope(NMS) in children,and to analyze the diagnostic value of ambulatory blood pressure pattern in children with NMS.Methods: Forty-seven children with NMS [20 males and 27 females,mean age(11.7?2.8) years] who came from Peking University First Hospital from July,2007 to March,2008 were included in the study.Twenty-three healthy children [12 males and 11 females,mean age(11.0?3.2) years] were recruited as control group.And the hemodynamic patterns of NMS were detected.Based on the hemodynamic patterns,they were divided into vasovagal syncope(VVS) group [16 children in total,7 males and 9 females,mean age(11.5?2.8) years] and postural tachycardia syndrome(POTS) group [31 children in total,13 males and 18 females,mean age(11.7?2.9) years].Parameters of children with different hemodynamic patterns in ambulatory blood pressure and diagnostic value of ambulatory blood pressure pattern were analyzed.SPSS 10.0 software was used for the statistical analysis of these data.Results: Mean diastolic pressure of the whole day,mean diastolic pressure in the day-time and mean systolic pressure at night in POTS group were higher than those of the control group,reapectively(P0.05).The systolic pressure differences in the day-time and at night in VVS group and POTS group were lower than those of the control group,respectively(P0.05).The non-spoon pattern rate of fluctuation curve of ambulatory blood pressure in VVS group and POTS group was higher than that of the control group(68.8% vs 17.4%,64.5% vs 17.4%,P0.05).The sensitivity,specificity and diagnostic coincidence of ambulatory blood pressure pattern to NMS was 66.0%,82.6% and 71.4%,respectively.Conclusion: There was autonomic nerve adjustment imbalance in children with NMS.And the diagnostic value of ambulatory blood pressure pattern to children with NMS was high.

OBJECTIVETo investigate the role of calcineurin (CaN) in the lung fibroblast proliferation and collagen synthesis induced by basic fibroblast growth factor (bFGF).

METHODSWe used Western blot and immunohistochemical methods for investigating the content and distribution of calcineurin in the lung tissue. Calcineurin activity in different tissues was measured using (32)P-labelled substrate. In the primary culture of lung fibroblasts, (3)H-thymidine ((3)H-TdR) and (3)H-proline incorporation methods were used to study the effect of cyclosporin A (CsA), an inhibitor of calcineurin, on the lung fibroblast DNA and collagen synthesis stimulated by bFGF.

RESULTSWe found that calcineurin was expressed in lung tissue and has phosphatase activity (7.1 +/- 2.0 pmol Pi/mg pr/min). CsA (10(-8) - 10(-6) mol/L) inhibited lung fibroblast (3)H-TdR incorporation induced by bFGF in a dose-dependent manner, with the inhibitory rates by 20%, 46% and 66% (P < 0.01). CsA (10(-7) - 10(-6) mol/L) inhibited (3)H-proline incorporation in lung fibroblasts stimulated by bFGF, with the inhibitory rates by 21% and 37% (P < 0.01). In a culture medium, CsA (10(-8) - 10(-6) mol/L) inhibited (3)H-proline secretion induced by bFGF in a dose-dependent manner, with the inhibitory rates by 19%, 29% (P < 0.05) and 56% (P < 0.01). CsA (10(-7) mol/L) could inhibit calcineurin activity by 44% in lung fibroblasts (P < 0.01).

CONCLUSIONSCalcineurin is expressed in lung tissue and has phosphatase activity. It is involved in the bFGF stimulated lung fibroblast DNA and collagen synthesis.

Animals ; Calcineurin ; analysis ; physiology ; Cell Division ; Cell Survival ; drug effects ; Collagen ; biosynthesis ; Fibroblast Growth Factor 2 ; pharmacology ; Fibroblasts ; drug effects ; physiology ; Lung ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

Aim To investigate the effect of urotensin Ⅱ on vascular calcification.Methods Calcified VSMCs of rat in vitro were induced by ?-glycerophosphate.Cellular calcium content,ALP activities,45Ca accumulation and osteocalcin content were measured.Results Compared with those of control group,calcium content,ALP activities,45Ca uptake and osteocalcin in calcified VSMCs increased greatly(P

Objective: To determine the role of cross-talk between calcineurin-dependent signal transduction pathway and protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) in airway remodeling in asthma. Methods: Male guinea pigs were sensitized with intraperitoneal injections of ovabumin (OVA), then treated with cyclosporin A (CsA,5 mg/kg), an inhibitor of calcineurin, then inhaled OVA for 2 weeks 14 days later. Activities of calcineurin, PKC, MAPK, and PKA were was analyzed by phosphorylation and dephosphorylation. In primary cultures of rat airway smooth muscle cells (ASMC), activities of calcineurin, PKC, MAPK, and cross-talk induced by urotensin Ⅱ (UⅡ), a recently identified strong mitogen, were measured. Results: (1) The activities of calcineurin, MAPK and PKC increased by 19% (P0.05). (4) CsA 10 -6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P0.05). Conclusion:The signal transduction pathways between calcineurin and other protein kinases such as PKC, MAPK and PKA have cross-talk in airway remodeling in asthma.

OBJECTIVETo investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty.

METHODSIn rat aortic artery restenosis model produced by denudation of aortic endothelia, we observed changes of endothelin (ET), angiotensin II (AII), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in plasma and aorta with radioimmunoassay and expression of hypertension-related gene (HRG-1) with semi-quantitative RT-PCR, and studied the effects of these peptides on intimal hyperplasia, intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore, in cultured cells, we studied the effects of these peptides on vascular smooth muscle cell (VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with 3H-TdR incorporation and RT-PCR respectively.

RESULTSAfter angioplasty, the levels of ET and AII in plasma and aorta significantly increased, accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty, the levels of ET in plasma and aorta increased by 69% and 124% respectively, compared with sham group (P < 0.01); and the level of aortic AII increased by 80% (P < 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme (ACE) could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group, on day 3 after angioplasty, the CGRP levels in plasma and aorta increased by 64% and 89% respectively (P < 0.01) and the Adm levels in plasma and tissue increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury (by 66% and 79% respectively, P < 0.01). In addition, ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase (MAPK) activity, while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.

CONCLUSIONSET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.

Adrenomedullin ; Angioplasty, Balloon ; adverse effects ; Angiotensin II ; pharmacology ; therapeutic use ; Animals ; Aorta, Thoracic ; cytology ; metabolism ; Calcitonin Gene-Related Peptide ; pharmacology ; therapeutic use ; Cell Division ; drug effects ; Cells, Cultured ; Coronary Restenosis ; etiology ; metabolism ; Endothelin-1 ; pharmacology ; therapeutic use ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; Muscle, Smooth, Vascular ; cytology ; Peptides ; pharmacology ; therapeutic use ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Wistar ; Vasodilator Agents ; pharmacology ; therapeutic use

Objective:To investigate the role of endogenous hydrogen sulfide(H2S)in patients with asthma.Methods:Levels of serum H2S,lung function and cell differential count in induced sputum were studied in 44 patients with acute exacerbation of asthma,33 patients with stable asthma and 12 health subjects.Of the 33 patients with stable asthma,3 failed to achieve induced sputum.Results:The serum H2S level was(75.2?13.0)?mol/L in controls(12 cases),(55.8?13.6)?mol/L in patients with stable asthma(33 cases),(57.8?6.3)?mol/L in patients with mild of acute exacerbation asthma(9 cases),(40.8?5.1)?mol/L in that with moderate of acute exacerbation asthma(13 cases),and(31.3?2.9)?mol/L in that with severe of acute exacerbation asthma(22 cases,F=44.592,P

Objective: To explore the effects of hydrogen sulfide (H 2S) on hypoxic pulmonary vascular smooth muscle cell (VSMC) apoptosis in rats. Methods: Twenty four Wistar rats were divided into 3 groups: control group ( n =8), hypoxia group ( n =8), and hypoxia +NaHS group ( n =8). The plasma level of H 2S was determined by methylene blue spectrophotometric method. VSMC apoptosis was measured by terminal deoxynucleotidyl transferase biotin nick end labeling (TUNEL). The protein expressions of Bcl 2, Fas and caspase 3 in pulmonary arteries were detected by immunohistochemical technique. Results: Compared with rats in the control group, the plasma level of H 2S decreased by 36% in rats of hypoxic group . The apoptotic rate per area in VSMCs detected with TUNEL was significantly decreased by 52.9% in rats of hypoxic group . The expressing integral score of Bcl 2 of VSMCs was increased by 123.9%,while Fas protein expression of VSMCs was decreased by 45% and caspase 3 protein expression of VSMCs was not significantly changed in rats of hypoxia group. But compared with rats in the hypoxia group, the plasma level of H 2S increased by 65% in rats of hypoxia+NaHS group. The apoptotic rate in VSMCs of TUNEL was significantly increased by 62.5% in rats of hypoxia+NaHS group. The Bcl 2 protein expression of VSMCs was decreased by 36.4% in rats of hypoxia+NaHS group. The expressing integral scores of Fas and caspase 3 were significantly higher in rats of hypoxia+NaHS group than in those of hypoxia group. Conclusion: Hypoxia decreased the pulmonary artery smooth muscle cell apoptosis. H 2S inhibited Bcl 2 protein expression of VSMCs and activated Fas and caspase-3 protein expressions of VSMCs, and therefore promoted the pulmonary artery smooth muscle cell apoptosis.