Haemodynamic changes in high altitude pulmonary edema and effects of oxygen breathing

AIM:To explore the pathogenic mechanism of high altitude pulmonary edema(HAPE).METHODS:Haemodynamic changes and effects of 100 percent oxygen breathing were measured by Swan-Ganz thermistor catheters, high altitude healthy volunteers were served as controls.RESULTS:The important features of haemodynamic changes in HAPE: (1)Pulmonary arterial pressure was raised; (2)Pulmonary arterial resistance and cardiac output were raised; (3)Pulmonary artery wedge pressures and right atrial pressure were normal; (4)Pulmonary arterial pressure and resistance were induced by oxygen breathing.CONCLUSIONS:The normal pulmonary artery wedge pressures with a high cardiac output indicated that HAPE was recognized as a form of noncardiogenic pulmonary edema. The pulmonary hypertension may play an important role in the development of HAPE.     

Ca2+-activated Cl- channels and pulmonary hypertension induced by high pulmonary blood flow

Pulmonary hypertension induced by high pulmonary blood flow involves a variety of complex mechanisms, including endothelial damage, pulmonary artery smooth muscle relaxation-contraction disorder and vascular remodeling. Besides, the factor of ion channels in pulmonary artery smooth muscle cells is also highly correlated to vasoconstriction. In recent years, many studies have shown that activation of Ca²⁺-activated Cl^- channels is responsible for the membrane depolarization of pulmonary artery smooth muscle cells, and plays an important role in the regulation of vascular tone and vasoconstriction. This article reviews the biophysical and pharmacological characteristics of Ca²⁺-activated Cl^- channels as well as the influence of Ca²⁺-activated Cl^- channels in high pulmonary blood flow-induced pulmonary hypertension.     

Alteration of pulmonary vascular structure and gaseous molecules in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To examine the alteration of pathologic structure and gaseous molecules in rats with pulmonary hypertension induced by high pulmonary blood flow.METHODS: Aortocaval shunting was produced for 11 weeks in rats, and pulmonary hemodynamics was evaluated.Pulmonary vascular micro- and ultra- structure was also examined.Meanwhile,the concentration of plasma nitric oxide (NO) and carbon monoxide (CO) was measured by spectrophotometry.The expression of endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in pulmonary arteries was detected by immunohistochemistry.RESULTS: After 11- week aortocaval shunting,pulmonary artery mean pressure was significantly increased.Muscularization of small pulmonary vessels and relative medial thickness and area of pulmonary arteries were obviously increased in shunting rats compared with controls.Ultrastructure of intrapulmonary arteries changed obviously in shunting rats.Meanwhile,plasma NO concentration was increased and eNOS expression in pulmonary artery endothelial cells was significantly augmented in rats of shunting group.Plasma carbon monoxide level and HO-1 expression in puomonary artery smooth muscle cells,however,were not altered in shunting rats.CONCLUSIONS: Pulmonary vascular structural remodeling is the important pathologic basis of pulmonary hypertension induced by a left-to-right shunt,and NO other than CO might play an important regulating role in the development of high pulmonary blood flow-induced pulmonary hypertension.     

Effect of nuclear factor kappa B inhibitor on the responsiveness of pulmonary artery rings to protein kinase C in rats with hypoxia-induced pulmonary hypertension

AIM: To investigate the role of nuclear factor kappa B (NF-κB) inhibitor in the responsiveness of isolated pulmonary artery rings to protein kinase C (PKC) in rats with hypoxia-induced pulmonary hypertension. METHODS: The pulmonary artery rings removed endothelium were prepared from model rats with hypoxia-induced pulmonary hypertension and control rats. The effects of PKC activator PMA (0.5 μmol/L) time-response cures and NF-κB inhibitor PDTC (0-1 000 μmol/L) concentration-response cures on pulmonary artery rings were observed. The responsiveness of each ring was tested by applying a maximally effective concentration of phenylephrine (10 μmol/L). Data were calculated as relative ratio by the maximally responseness ( P₀ ) setting at 100%, and the relative responseness tensions to PMA and PDTC were derived by dividing by the counts in P₀. t_1/2 and T show the time achieving half-maximal response and lasting maxima response to 0.5 μmol/L PMA, respectively. RESULTS: mPAP and RV/(LV+S)in hypoxia group were greater than those in control group(P<0.05).For the responseness of the artery rings to PMA of 0.5 mol/L,the relat ive tensions of hypoxia group were significantly higher(P<0.05)as compared with respective controls;mean t_1/2 in hypoxia group was shorter than that in control group(P<0.05).Mean T in hypoxia group was longer than that in control group(P<0.05).For the relative tensions of the artery rings to PDTC and PMA,hypoxia group were higher than those of controls in the range of PDTC 0-100 mol/L(P<0.05);the relative tensions of two group significantly decreased beyond PDTC of 500 mol/L(P<0.05). CONCLUSIONS: The responsiveness of pulmonary artery rings to PMA was increased during hypoxia and decreased to PDTC in concentration-dependent manner. These results further suggest that changes of PKC－NF-κB signaling pathway of pulmonary artery smooth muscle cells may be involved in vasoconstriction of hypoxia-induced pulmonary hypertension.     

Impact of hydrogen sulfide donor on endothelin-1 and connective tissue growth factor expression in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To explore the possible impact of hydrogen sulfide (H2S) donor-sodium hydrosulfide (NaHS) on endothelin-1 (ET-1) and connective tissue growth factor (CTGF) expressions in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty-two male SD rats were randomly divided into 4 groups: shunt group, shunt+NaHS group, sham group and sham+NaHS group. Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 11 weeks of experiment, rat systolic pulmonary artery pressure (SPAP), lung tissue H2S, plasma ET-1 concentration and lung tissue ET-1mRNA expression, as well as pulmonary artery CTGF protein expression were detected.RESULTS: After 11 weeks of experiment, SPAP, lung tissue ET-1mRNA, plasma ET-1 as well as pulmonary artery CTGF expressions were increased markedly, respectively, whereas H2S in lung tissue decreased significantly in rats of shunt group as compared with that in sham group (all P<0.05). After administration of NaHS for 11 weeks, H2S in lung tissue increased significantly, whereas SPAP, plasma ET-1 and lung tissue ET-1 mRNA expression as well as pulmonary artery CTGF protein expression decreased significantly, respectively, in rats of shunt+NaHS group as compared with that in shunt group (all P<0.05).CONCLUSION: NaHS might be involved in the development of pulmonary hypertension induced by high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expressions in lung tissues of rats.     

Hypoxia simulated to high altitude promotes right ventricular ACE2 activity in adult SD rats independent of pulmonary artery hypertension

AIM: To determine the right ventricular angiotensin converting enzyme2 (ACE2) activity in adult SD rats under normoxia and hypoxia environment, and to detect the relationship between ACE2 and high altitude heart disease initially. METHODS: Adult male Sprague Dawley (SD) rats were raised under hypoxia environment simulated to high altitude (5 000 m, 23 h/d), then divided into hypoxia 1 d, 15 d and 30 d groups randomly. The control group was set up under normoxia environment. The right ventricular function, ponderal index, pulmonary artery pressure and right ventricular ACE2 activity were determined. The effect of captopril or nitrendpine on cardiac ACE2 activity in hypoxia 30 d group was also observed. RESULTS: The dramatic up-regulation of cardiac ACE2 expression of mRNA and protein and its activity in hypoxia 30 d group was observed, together with obvious increase in right ventricular function, ponderal index and pulmonary artery pressure. Although captopril or nitrendipine depressed pulmonary artery pressure and cardiac function dramatically, no significant alteration of right ventricular ACE2 activity was detected. CONCLUSION: Chronic hypoxic exposure promotes the ACE2 expression and activity in right ventricular, indicating that ACE2 may be correlated to the changes of cardiac architecture and function induced by hypoxia. Up-regulation of ACE2 expression maybe contribute to the increase in right ventricular ACE2 activity, and pulmonary artery hypertension may not be the main reason for the changes of ACE2 activity under hypoxia environment.     

Effects of hypoxia and hypercapnia on expression of soluble guanylate cyclase in rat pulmonary artery

AIM:To investigate the expression of soluble guanylate cyclase protein and its mRNA in rat pulmonary artery after exposure to hypoxia and hypercapnia.METHODS:Male Sprague-Dawley rats were randomly split into 4 group, which were hypoxic hypercapnic (HH 1 week, HH 2 weeks, HH 4 weeks) group and control group, to copy pulmonary hypertensive animal model. The expression of sGCα₁ and β₁ subunits protein of medial and small pulmonary artery was performed by immunohistochemistry with a polycolonal antibody. In situ hybridization was performed on the rat lung tissue using sGC oligonuclear probe to assay the expression of sGCα₁subunit mRNA.RESULTS:The sGCα₁ and β₁ subunits protein and sGCα₁ subunit mRNA were faint staining in the pulmonary small and medium artery in HH1 week, HH 2 weeks and HH 4 weeks groups compared with control group (all P＜0.01).CONCLUSION:sGC subunit mRNA and protein expression in pulmonary small and medium artery were decreased after exposure to hypoxia and hypercapnia, which took part in the development of the pulmonary hypertension.     

Expression of voltage-gated potassium channel gene of pulmonary artery smooth muscle cells in COPD merge chronic hypoxic patients

AIM: To study the change of expressions of Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv3.1 genes in pulmonary artery smooth muscle cells (PASMCs) on COPD merge chronic hypoxic patients. METHODS: Human lung tissue was collected from surgical patients. RT-PCR technique was used to study the expression of Kv1.2, Kv1.3, Kv1.5, Kv2.1 and Kv3.1 genes. PASMCs were divided into two groups: ① PASMCs from normal human pulmonary artery, pure COPD patients and COPD merger chronic hypoxic patients pulmonary artery； ② Cultured PASMCs exposed to continual chronic hypoxia or normoxia. RESULTS: ① The expression of Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv3.1 encoding genes were found in human PASMCs exposed to either normixa or chronic hypoxia. ② The expression of Kv1.2, Kv1.5, Kv2.1 genes in PASMCs exposed to chronic hypoxia were significantly decreased compared with control groups (P<0.05). ③ The expression of Kv1.3, Kv3.1 genes in PASMCs exposed to chronic hypoxia showed no significant change compared with control groups (P>0.05). ④ The expression of Kv1.2, Kv1.5, Kv2.1, Kv3.1 genes in pure COPD patients were significantly increased compared with control groups (P<0.05). CONCLUSIONS: ①The results suggested that Kv1.2, Kv1.5, Kv2.1 genes may be oxygen sensitive gene. Their expressions are affected by chronic hypoxia, which probably play an important role in human pulmonary artery hypertension. ② Kv1.3, Kv3.1 genes may not be oxygen sensitive gene and their expression are not affected by chronic hypoxia, which might play a secondary role in human pulmonary artery hypertension.     

The Progress in The Plexiform Lesion of Pulmonary Hypertension

Pulmonary arterial hypertension is defined as a multifactorial group of pulmonary vascular disorders characterized by a progressive increase in the pulmonary vascular resistance, resulting in right heart failure and premature death. The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. This article summarized the recent progress in the plexiform lesion including its occurrence, structure, animal models and molecular mechanism, which tried to predict the tendency of plexiform lesion study.     

Effects of acute hypoxia on calcium signal of sarcoplasmic reticulum in pulmonary artery smooth muscle in rats

AIM: To investigate the effects of acute hypoxia on calcium of sarcoplasmic reticulum in pulmonary artery smooth muscle in rats. METHODS: The fluorescence Ca2+ indicator Fura-2/AM was used to observe intracellular free Ca2+ concentration (［Ca2+］i) in rat pulmonary artery smooth muscle cells (PASMCs) in the presence of ryanodine (RD) and cyclopiazonic acid (CPA) in normal (37 ℃, 5%CO2, 21%O2, 74%N2), acute hypoxic (37 ℃, 5%CO2, 2%O2, 93%N2) under Ca2+ and Ca2+ free conditions. Pulmonary artery ring was used to determine the pulmonary artery tension by using routine blood vascular perfusion in vitro under the same conditions. RESULTS: (1) Under acute hypoxic conditions, ［Ca2+］i was increased ［(96.99±7.16) nmol/L in normoxic condition and (257.06±32.48) nmol/L in hypoxic condition, P<0.01］. (2) Ryanodine or procain, an agent that blocks ryanodine receptor-seneitive (RyR) Ca2+ stores, inhibited hypoxia-induced increases in ［Ca2+］i { ［Ca2+］i decreased to (100.91±11.21) nmol/L, P<0.01}. CPA or thapsigargin (TG), the agent that inhibits sarcoplasmic reticulum (SR) Ca2+ -ATPase and inhibits SR uptake Ca2+, increased ［Ca2+］i. Under acute hypoxic and Ca2+ conditions, CPA or thapsigargin (TG) increased ［Ca2+］i more than that in Ca2+ free conditions. (3) Acute hypoxia evoked pulmonary artery contractions. Pulmonary artery tension had no effects under normoxic and increased under acute hypoxia condition. (4) Ryanodine or procain inhibited hypoxia-evoked contractions in the pulmonary artery. CPA or TG increased artery tension. Under acute hypoxic and Ca2+ conditions, CPA or TG increased tension more than that in Ca2+ free condition. CONCLUSION: The results indicate that release of Ca2+ from the SR, at least, RyR Ca2+ store, contributes to the mechanism of hypoxic pulmonary vasoconstriction in rat. This is a mechanism intrinsic to pulmonary artery without the need for Ca2+ influx across the plasmalemma or an endothelial factor.     

The acute inhibitory effect of adrenomedullin on hypoxia-induced pulmonary hypertension in rats

AIM:The aim of this study is to investigate the acute inhibitory effects of adrenomedullin(ADM_1-52) on hypoxia pulmonary hypertension and its influence on systemic blood pressure.METHODS:Thirty-six male Wistar rats were divided into two groups. Eighteen were exposed to hypoxia for 21 days as hypoxic pulmonary hypertension group,and another eighteen were kept in ambient as control group. Each group were divided into three subgroups which were injected intravenously with ADM 0.1 nmol/kg, 0.3 nmol/kg, 1 nmol/kg, respectively,then hemodynamic parameters were recorded. Plasma cyclic adenosine 3,5,-monophosphate (cAMP) was measured by radioimmunoassay before,during and after injection of 0.3nmol/kg adrenomedullin(ADM_1-52).RESULTS:Mean pulmonary arterial pressure (mPAP)in the hypoxia and control rats treated with ADM decreased, the fall in hypoxia rats is more obviously than control(P＜0.05), ADM (0.1-0.3 nmol/kg) produced dose-related reductions in mPAP in hypoxia rats(P＜0.05). Mean systemic blood pressure(mSBP) of the rats in both groups decreased in a does-dependent manner, and it was more obvious in control rats. Plasma cAMP is higher in hypoxia group than that in control group.CONCLUSION:ADM depresses the rat hypoxia pulmonary hypertension in short term through, at least partly, cAMP-dependent mechanism.     

Effect of chronic cigarette smoking on BKCa and Kv1.5 expression in rat pulmonary arterial smooth muscle cells

AIM:To investigate the role of potassium channel expression alteration in chronic cigarette smoking-induced increase in pulmonary vascular responsiveness, the effect of chronic cigarette smoking on large-conductance calcium-activated potassium channel (BK_Ca) and voltage-dependent delayed rectifier potassium channel (Kv1.5) expression in rat pulmonary smooth muscle cells were investigated in vivo. METHODS:HE staining, immuno-histochemistry and in situ hybridization techniques were used. RESULTS: (1) Chronic cigarette smoking downregulates the protein and mRNA expression of BK_Ca in pulmonary arterial smooth muscles. (2) Chronic cigarette smoking downregulated the protein and mRNA expression of Kv1.5 in pulmonary arterial smooth muscles. (3) In big artery, BK_Ca decreased more makedly than Kv1.5, but in small artery, both of them decreased equally. CONCLUSION:Chronic cigarette smoking downregulates the levels of BK_Ca and Kv1.5 in rat pulmonary arterial smooth muscle cells in vivo, which maybe contribute to the mechanism of cigarette smoking-induced increase in pulmonary vascular responsiveness.     

p38 MAPK specific inhibitor SB203580 down-regulates acute pulmonary thromboembolism-induced pulmonary artery hypertension and monocyte chemoattractant protein-1 in rats

AIM：To explore the hypothesis that initiation of pulmonary hypertension involves the up-regulation of monocyte chemoattractant protein-1 (MCP-1) in acute pulmonary thromboembolism (PTE), and to evaluate the role of p38 mitogen-activated protein kinase (MAPK) in this process. METHODS：One hundred and fifty male SD rats were randomly divided into five groups (n=30): normal control group, solvent control group, acute PTE group, acute PTE plus SB203580 (a p38 MAPK specific inhibitor) pretreatment group and acute PTE plus C1142 (a rodent chimeric monoclonal antibody neutralizing rat MCP-1) pretreatment group. Thirty rats in each group were further divided into 1, 4 and 8 h subgroups (n=10). A rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. SB203580 or C1142, dissolved in 1% dimethyl sulfoxide (DMSO), was administered to the animals through caudal vein 1 h prior to the beginning of acute PTE modeling. Rats in normal control group and solvent control group were injected with normal saline and 1% DMSO, respectively. The mean pulmonary artery pressure (MPAP) and the mRNA and protein expression of MCP-1 were measured at each time point. RESULTS：Acute PTE elicited significant increase in MPAP, and up-regulated the expression of MCP-1. Pretreatment with SB203580 or C1142 significantly reduced MPAP, and down-regulated the expression of MCP-1. CONCLUSION：These findings suggest that MCP-1 is involved in the formation of acute PTE-induced pulmonary hypertension, and SB203580 down-regulates the expression of MCP-1 via p38 MAPK signaling pathway, thus attenuating pulmonary hypertension.     

Effect of exogenous HGF gene transfection on pulmonary perfusion and pressure in pulmonary artery hypertension in rabbits

AIM: To investigate the feasibility of exogenous hepatocyte growth factor (HGF) gene transfection to promote pulmonary collateral angiogenesis, improve pulmonary perfusion and reduce pulmonary artery pressure in the rabbit model of pulmonary artery hypertension (PAH). METHODS: The model rabbits of PAH were randomly divided into control group, empty vector group and HGF gene transfection group. The rabbits in HGF gene transfection group were transfected with Ad-HGF via intratracheal instillation. Pulmonary hemodynamic indicators were monitored in the 4th week after HGF gene transfection. Density of pulmonary vessels was examined with double-labeling immunofluorescence (endothelial cells were labeled with anti-FⅧ and vascular smooth muscle cells were marked with anti-α-SMA). Double-labeling immunofluorescence of FITC-lectin and anti-α-SMA was also performed to evaluate the pulmonary blood perfusion. RESULTS: Four weeks after transfection, the density of pulmonary arterioles of the rabbits in HGF gene transfection group was higher than that in control group and empty vector group (P<0.05), which was confirmed by double-labeling immunofluorescence. Pulmonary blood perfusion in HGF group was significantly increased compared with that in the other two groups, in which pulmonary arterial stenosis and occlusion were observed. The mean pulmonary artery pressure in HGF transfection group was much lower than that in control group and empty vector group (P<0.05). CONCLUSION: Four weeks after intratracheal adenoviral-mediated HGF gene transfection, pulmonary collateral vessels and pulmonary perfusion increase, and the pulmonary artery pressure is effectively reduced.     

Effect of hypercapnia on lysyl oxidase-dependent collagen cross-linking and hypoxia-induced pulmonary hypertension in rat

AIM: To investigate the effect of hypercapnia on hypoxia-induced pulmonary hypertension and the changes of lysyl oxidase (LOX) and extracellular matrix collagen cross-links in the rat. METHODS: Sprague-Dawley rats were randomly divided into 4 groups:normoxia group, hypoxia group, hypercapnia group and hypoxia+hypercapnia group. LOX activity was detected by fluorescence spectrophotometry. LOX protein expression was detected by immunohistochemistry and Western blot. The mRNA expression of LOX in the pulmonary artery was detected by real-time PCR. RESULTS: The levels of mean pulmonary artery pressure (mPAP), RV/(LV+S) and WA/TA in hypoxia group were significantly higher than those in normoxia group (P<0.01). Moreover, the levels of mPAP and RV/(LV+S) in hypoxia+hypercapnia group were significantly lower than those in hypoxia group (P<0.01). However, no significant difference of mPAP and RV/(LV+S) between hypercapnia group and normoxia group was observed. In hypoxia group, the collagen cross-links in the lung tissue was significantly higher than that in normoxia group and hypercapnia group (P<0.01). Importantly, collagen cross-links in the lung tissue of hypoxia+hypercapnia group was significantly lower than that in hypoxia group (P<0.01). There was no significant difference in collagen cross-links between hypercapnia group and normoxia group. The expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries of hypoxia group were significantly increased as compared with normoxia group (P<0.01). Furthermore, the expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries in hypoxia+hypercapnia group were lower than those in hypoxia group (P<0.01). CONCLUSION: Hypoxia not only up-regulates LOX but also promotes collagen cross-linking in the rat lung, which contributes to the development of pulmonary hypertension. Hypercapnia inhibits hypoxia-induced LOX expression and collagen cross-linking, therefore impairing the progress in hypoxia-induced pulmonary hypertension.     

Effects of endogenous carbon monoxide on the expression of transforming growth factor-beta 3 and type Ⅰ collagen of pulmonary artery in rats under hypoxia

AIM: To explore the impact of endogenous carbon monoxide (CO) on the expression of transforming growth factor-beta 3 (TGF-β₃) and type Ⅰcollagen in pulmonary artery of rats under hypoxia. METHODS: In the model of rats under hypoxic pulmonary hypertension, the measurement of pulmonary artery mean pressure (PAMP) and carboxyhemoglobin (HbCO) formation within pulmonary tissue homogenates was performed. TGF-β₃ and collagen Ⅰexpressions were detected by immunohistochemical assay. The expressions of TGF-β₃, type Ⅰ procollagen mRNA, and tissue inhibitor of metalloproteinase -1 (TIMP-1) mRNA were detected by in situ hybridization. RESULTS: ZnPP significantly increased PAMP and markedly decreased HbCO formation within lung tissue homogenates in rats under hypoxia( P< 0.01). Meanwhile, ZnPP promoted the expression of TGF-β₃ and collagen Ⅰprotein in pulmonary arteries in rats under hypoxia ( P< 0.01). ZnPP obviously elevated the expressions of TGF-β₃ mRNA, type Ⅰ procollagen mRNA, and TIMP-1 mRNA in pulmonary arteries in rats under hypoxia ( P< 0.01). CONCLUSION: Endogenous CO plays an important role in decreasing collagen synthesis and promoting degradation in pulmonary artery of rats under hypoxia by inhibiting the expression of TGF-β₃.     

Effect of endogenous H2S on pulmonary hypertension during acute lung injury induced by LPS and its interaction with NO

AIM: To investigate the effect of H2S on pulmonary artery hypertension during acute lung injury induced by LPS and the interaction between the systems of hydrogen sulfide (H2S)/cystathionine-β-lyase (CSE) and nitric oxide (NO)/nitric oxide synthase (NOS) in this process. METHODS: Seventy-two adult male rats were randomly divided into four groups: control group, LPS group, LPS+L-NAME group and LPS+propargylglycine (PPG) group. Mean pulmonary artery pressure (mPAP) of each rat was examined at 2 h, 4 h, 6 h and 8 h after treatment. H2S and NO contents in plasma, NO content, iNOS, cNOS and CSE activity in lung were measured at 4 h or 8 h after treatment, respectively. Expression of iNOS in lung tissue was also detected by immunohistochemistry technique, and the injury of lung was evaluated with morphological changes under microscope. RESULTS: LPS could induce severe lung injury, and mPAP, NO content, iNOS activity and its protein expression in LPS group significantly increased, but cNOS activity, H2S content and CSE activity decreased compared with those of control group. Administration of L-NAME before LPS could attenuate the changes induced by LPS. Pre-administration of PPG, a CSE inhibitor, exacerbated the injury by LPS, but there was no prominent variation in cNOS activity. CONCLUSION: Reduced endogenous H2S could increase pulmonary artery hypertension during acute lung injury induced by LPS. There is a negative effect between H2S/CSE system and NO/NOS system in this process.