Biomedical subjects

Bin Geng

Publications and source records attributed to Bin Geng.

At least 19 recordsLinked to original sources

PubMed2006

Endoplasmic reticulum stress response is involved in the pathogenesis of stress induced gastric lesions in rats.

Stress gastric ulcer is a serious complication, but the mechanism involved is not fully clarified. It is well known that mucosal cell apoptosis plays a crucial role in the pathogenesis of gastric ulceration. Recent studies have shown that endoplasmic reticulum (ER) stress is an important pathway leading to cellular apoptosis. To investigate the role of ER stress in the pathogenesis of stress gastric ulcer, we studied the alteration in the expression of ER stress markers GRP78 (glucose-regulated protein 78) and caspase-12 (an ER stress-specific proapoptotic molecule) and their relations with gastric mucosal apoptosis during development of stress gastric lesions in the water-immersion and restraint stress (WRS) model in rats. Rats developed severe gastric lesions after 6 h of WRS. Typical apoptosis was observed at the edge cells of WRS induced gastric lesions. Western blot analysis showed that GRP78 and activated caspase-12 were over-expressed in the gastric tissues of WRS rats. Immunohistochemical analysis demonstrated that increased GRP78 and caspase-12 were distributed only under the lesions. In addition, dithiothreitol and tunicamycin (ER stress inducers), which increased the expression of GRP78 and activated caspase-12, caused gastric mucosal injury and mucosal cell apoptosis in vitro. These findings suggest that ER stress might be involved in the development of stress gastric ulcer through an apoptotic mechanism.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

[Restraint stress down-regulates L-Arg/NOS/NO pathway of platelet and aortic intima in rats].

OBJECTIVE: To investigate alteration and cross link of the aortic intima and platelet endogenous L-Arg/NOS/NO pathway induced by water immersion restraint (WIR) stress. METHODS: After 7 h of WIR stress, the aortic intima was isolated and prepared the platelet, then NO2- production released from aortic intima and platelet was measured with Greiss regent, NOS activity and L-arginine transport activity were detected by isotope tracer method. RESULTS: After 7 h of WIR stress, the levels of NO2- from platelet and aortic intima obviously decreased by 57% and 46% respectively as compared with the control rats (P<0.01). The inhibitory effects of NO2- showed a positive correlation between platelet and aortic intima by person regression analysis (r2=0.9835, P<0.01). The kinetics analysis of NOS activity of platelet showed that the enzymatic catalytic maximum velocity (Vmax) decreased by 44%, Km values increase by 18% and the enzymatic catalytic efficiency was obviously reduced in the WIR stress rats (P<0.01). The aortic intima NOS activity was inhibited by 50% after WIR stress (P<0.01). The person analysis showed the obvious correlation between them (r2=0.9726, P<0.01). In the WIR stress platelet, the L-Arg transport Vmax obviously reduced by 32%, Km parameter increased 37%, and the transport efficiency was inhibited by 50% (P<0.01), which exhibited obvious positive correlation with the inhibition of L-Arg transport activity in aortic intima (27%) of WIR stress rats (r2=0.9887, P<0.01). CONCLUSION: WIR stress down-regulated endogenous L-Arg/NOS/NO pathway of aortic intima and platelet, whose alteration showed obvious positive correlation. Detection of the alteration of endogenous L-Arg/NOS/NO pathway in platelet might act as an indirect method to assess the endothelial dysfunction involving the pathogensis of stress.

Animals↗

PubMed2006

[Simvastatin inhibits hypertension-induced cardiac hypertrophy in rats through activation of heme oxygenase-1/carbon monoxide pathway].

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d) by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d) intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index (LVMI), the content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes, simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1) mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake induced by angiotensin II in a concentration-dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.

Angiotensins↗

PubMed2006

[Effect of hydrogen sulfide on Bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: To explore the change of endogenous hydrogen sulfide and the effect of exogenously applied H(2)S on Bleomycin-induced pulmonary fibrosis in rats. METHODS: (1) Forty-eight male Wistar rats were randomly divided into control group, fibrosis group, fibrosis+NaHS-low group (1.4 micromol/kg, bid intraperitoneally) and fibrosis+NaHS-high group (7.0 micromol/kg, bid intraperitoneally). Pulmonary fibrosis was induced by intratracheal instillation of bleomycin. The control group and pulmonary fibrosis group were injected with the same volume of normal saline. Pulmonary pathology changes were observed, the plasma H(2)S concentration,the activity of CSE in lung tissue and the contents of MDA, hydroxyproline were detected on the 7th and 28th days respectively after bleomycin administration. CSE mRNA was also measured using quantitative RT-PCR. (2) Isolated lung tissues were exposed to Fe(2+)/H(2)O(2) without or with different concentrations of NaHS (10(-5), 5 x 10(-5), 10(-4), 10(-3) mmol/L) at 37 degree Celsius for 10 minutes, and the MDA content was assayed by biochemical method. RESULTS: (1) Compared with rats in control group, the concentration of plasma H(2)S and the activity of CSE in lung tissues in fibrosis group decreased on day 7 (all P<0.01); On the 28th day, the level of plasma H(2)S increased clearly (P<0.01) and the activity of CSE was ascendant without significant difference compared with that of control group. Relative CSE mRNA amounts in lung tissues increased 34%, 144%, respectively (all P<0.01) in rats of fibrosis group compared with those of control group. The contents of MDA and hydroxyproline increased significantly in fibrosis group compared with those of control group on days 7, 28 (all P<0.01). In NaHS-low group and NaHS-high group, the contents of MDA and hydroxyproline decreased markedly (all P<0.01). (2) The contents of MDA in incubation of lung tissues at different concentrations of NaHS were all decreased as compared with those in incubation with Fe(2+)/H(2)O(2) alone (all P<0.01). When NaHS was at 10(-4) mol/L, the MDA content reversed to the lowest value, which had the highest value at 10(-3) mol/L of NaHS. CONCLUSION: Endogenous CSE/H(2)S pathway was involved in the pathogenesis of rat pulmonary fibrosis. Exogenously applied H(2)S could attenuate the process of pulmonary fibrosis possibly because of reducing oxidative stress.

Animals↗

PubMed2006

Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats.

AIM: To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo. METHODS: A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, 45Ca2+ accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured. RESULTS: von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45Ca2+ accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P<0.01). Expression of the CSE gene was downregulated. However, calcium content, 45Ca2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45Ca2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P<0.01), and the calcium content and deposition of 45Ca2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P<0.01). The expression of the OPN gene was downregulated. CONCLUSION: The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.

Animals↗

PubMed2005

[Lysophosphatidic acid activates L-arginine/nitric oxide pathway of platelets in rats].

OBJECTIVE: To investigate the mechanism of platelet function caused by Lysophosphatidic acid (LPA), by observing the change of the L-arginine/nitric oxide synthase/nitric oxide (L-Arg/NOS/NO) pathway of platelet in rats. METHODS: LPA (10(-6), 10(-5) and 5x10(-5) mol/L) was administrated in rats and incubated for 30 and 60 minutes. The nitrite production was measured by Greiss assay; NOS activities and L-arginine transportation were detected by isotope tracer method and intracellular [Ca(2+)]i changes by fluorescent probe. RESULTS: LPA increased NO release by 35% and 56%, after incubating for 30 and 60 minutes, respectively. LPA (10(-6), 10(-5)aand 5x10(-5) mol/L) enhanced the NO productions of platelets in a concentration-dependent manner (P<0.01). EC(50) was 17.8 micromol/L, and 95% CI was 13.3-24.2 micromol/L, involved in the physiological concentration of LPA in plasma (P<0.01). Simultaneously, different doses of LPA increased NOS activities and L-arginine uptake in a dose-dependent manner (P<0.01). In this study, LPA (50 micromol/L) increased the intracellular free calcium ion concentration ([Ca(2+)]i, P<0.01), after incubating for 30 and 60 minutes. Pre-treated with NOS inhibitor-L-NAME for 20 minutes, LPA obviously enhanced the effects by 20% and 32% respectively (P<0.01). On the contrary, pre-treated with L-arginine (200 micromol/L) for the same times obviously reduced the effects by 14% and 18% respectively (P<0.01). CONCLUSION: LPA increased NO release by enhancing L-arginine uptake and NOS activities, up-regulating L-arginine/NOS/NO pathway in platelets of rats.

Animals↗

PubMed2005

Apelin protects myocardial injury induced by isoproterenol in rats.

We aimed to explore the change in level of apelin and its receptor APJ during myocardial injury and the therapeutic effects of apelin in myocardial injury. Rat myocardial injury was induced by subcutaneous injection of a high dose of isoproterenol (ISO); apelin and APJ mRNA levels were determined by RT-PCR; APJ protein was determined by Western blot; EIA and RIA were used to measure the apelin content and receptor binding, respectively. Plasma lactate dehydrogenase (LDH) activity and myocardial and plasma malondialdehyde (MDA) contents were higher in ISO-treated hearts than that in controls. ISO-treated rats showed lower +/-LV dp/dt(max) values and higher LVEDP value (all P<0.01), which suggested severe heart failure. As well, the apelin content in plasma, atrial and ventricular myocardium was decreased by 27%, 30% and 25% (P<0.01), respectively. The mRNA levels of apelin and APJ in myocardia were also markedly reduced; but the APJ protein level in myocardia was increased. However, administration of apelin significantly ameliorated myocardial injury and ISO-induced heart failure. Compared with the ISO-alone group, the group given low-dosage apelin (5 nmol/kg/day) had 39% and 66% higher +LV dp/dt(max) and -LV dp/dt(max) values, and 40.7% lower LVEDP value (P<0.01), and the leakage of myocardial LDH and increased MDA content were attenuated (all P<0.01). Interestingly, bolus injections of apelin (10 nmol/kg/day) resulted in potent inotropic effects in ISO-treated rats. ISO-induced myocardial injury resulted in hypoexpression of apelin and its receptor APJ, and the administration of exogenous apelin ameliorated heart failure and myocardial injury. Apelin could have a cardioprotective effect, and the apelin-APJ system may be a new therapeutic target in myocardial injury and heart failure.

Animals↗

PubMed2005

[Application of sensitive sulphur electrode assay to measure and analyze cystathionine-gamma-lyase/hydrogen sulfide pathway of cardiovascular tissues, cells and plasma in rats].

OBJECTIVE: To construct a method of measurement microamount hydrogen sulfide (H(2)S) using sensitive sulphur electrode. METHODS: According to the physical and chemical characters of H(2)S, H(2)S, which in the fluids by mean of physical dissolve and chemical shape, is turned to sulphur ion (S(2-)) by chemical responses. After the microamount of S(2-) was measured by sensitive sulphur electrode, and the concentration of H(2)S was converted, a method was constructed to measure the H(2)S. It was used to analyze the concentrations of H(2)S of plasma in rats and humans, the endogenous concentration of H(2)S of cardiovascular tissue in rats, and CSE activity of cardiovascular tissues and cells. RESULTS: The exponential regression of S(2-) in the extent including 1 to 80 micromol/L was found using sensitive sulphur electrode. The H(2)S levels of plasma in male and female rats were 40+/-4 and 41+/-5 micromol/L, respectively, and significant difference was not found; those in venous blood plasma of men and women were 33+/-4 micromol/L and 35+/-5 micromol/L respectively, without significant difference. There were not significant differences in the aortic endogenous levels of H(2)S (24+/-6 and 25+/-5 nmol/mg pro) and myocardial levels (19+/-4 and 19+/-6 nmol/mg protein) between female and male rats. There were no different results of CSE activity in aortal tissue using sensitive sulphur electrode or traditional methods, however, the CSE activity of vascular smooth muscle cells could be accurately measured using sensitive sulphur electrode, which was difficult in using traditional method. CONCLUSION: The sensitive sulphur electrode assay was fit for the analysis of CSE/H(2)S pathway in cardiovascular research.

Animals↗

PubMed2005

Adrenomedullin(27-52) inhibits vascular calcification in rats.

Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P<0.01), did not effect on calcium content (P>0.05), reduced 44.4% calcium uptake (P<0.01), lowered 21.1% alkaline phosphatase activity (P<0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P<0.01), taken from 55.5% calcium content (P<0.01), did not affect calcium uptake (P>0.05), inhibited 22.5% alkaline phosphatase activity (P<0.01), and restrained 21.9% osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P<0.01) and in receding vascular calcific nodules (18.6%, P<0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P<0.01) and in reducing calcium uptake (11.4%, P<0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P<0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.

Adrenomedullin↗

PubMed2005

[A new strategy to treat hyperhomocysteinemia].

Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. At present, the main therapeutic provision is to supply vitamin B(6), B(12) and folic acids, and the toxic and ill effect have been reported. Homocysteine, taurine, hydrogen sulfide and metallothionein are metabolic products from methionine. Homocysteine induces necrosis of endothelium, proliferation of vascular smooth muscle cells, proliferation and activation of vascular fibroblast cells and mitochondrial structural destruction and dysfunction of myocardium cells. Taurine, an end metabolic product of homocysteine, obviously reduces cardiovascular injury induced by homocysteine. The possible mechanism of antagonism by reducing oxidative stress and endoplasmic reticulum stress has been proved. Hydrogen sulfide, another end metabolic product of homocysteine, obviously reducing cardiovascular injury of homocysteine by scavenging oxidative radicals has been found. Metallothionein a derivant production of homocysteine metabolism, antagonism to homocysteine injury to cardiovascular system been discussed. Homocysteine, taurine, hydrogen sulfide and metallothionein, as a metabolic product of methionine, interactive antagonism and interactive biological influence have been reviewed. Induced endogenous or exogenous supply of taurine, hydrogen sulfide and metallothionein might resist cardiovascular injury induced by hyperhomocysteinemia. According to the methionine metabolic cycle, using endogenous antagonistic substances might be a new clinical preventive and treatment target of homocystinemia.

Animals↗

PubMed2005

Adrenomedullin induces heme oxygenase-1 gene expression and cGMP formation in rat vascular smooth muscle cells.

Adrenomedullin (ADM) is a potent vasodilatory peptide. It regulates blood pressure by increasing cyclic adenosine monophosphate (cAMP) and guanosine-3',5'-monophosphate (cGMP). We sought to investigate the effect of ADM on heme oxygenase-1 (HO-1) gene expression and cGMP formation in cultured rat vascular smooth muscle cells (VSMCs). ADM treatment, 10(-9) and 10(-8) mol/L, increased cGMP production, and it increased the intracellular cGMP content of platelets coincubated with VSMCs. It increased cGMP content by 158.8% and 273.5%, respectively; increased HO-1 activity by 49.5% and 87%, respectively; augmented HO-1 protein levels by 66% and 126%, respectively; upregulated the steady-state level of HO-1 mRNA by 73% and 159%, respectively, and increased HO-1 mRNA transcription synthesis by four- and seven-fold, respectively. These results suggest that ADM induces HO-1 gene expression and cGMP formation in rat VSMCs.

Adrenomedullin↗

PubMed2005

Effect of relaxin on myocardial ischemia injury induced by isoproterenol.

The omnipresent 6-kDa polypeptide relaxin (RLX) is emerging as a multifunctional endocrine and paracrine factor in a broad range of target tissues including cardiovascular tissues. To explore the pathophysiological roles of RLX in ischemic cardiovascular diseases, we studied the changes in RLX mRNA level in the myocardium and the effect of RLX supplements in rats with isoproterenol (ISO)-induced myocardial injury. In ISO-treated rats, RLX levels in myocardia and plasma increased 3.7- and 6.9-fold, respectively (P<0.01), the mRNA level increased significantly in myocardia compared with controls. Co-administration of RLX (0.2 and 2.0 microg/kg/d) and ISO increased left-ventricular pressure development and decreased left ventricular end-diastolic pressure (LVDEP) (all P<0.01). Malondialdehyde content in myocardia and lactate dehydrogenase and creatine phosphokinase activities in plasma in RLX-treated rats decreased markedly compared with that in ISO-treated alone rats (P<0.01 or P<0.05). In the high-dose RLX group, fibroblastic hyperplasia was relieved in myocardia, hydroxyproline level was lower, by 33% (P<0.05), and endothelin content in plasma was lower, by 31% (P<0.01) than in the ISO-alone group. Compared with control group, any indexes in sham rats treated with high-dose RLX were unaltered (all P>0.05). These results showed an up-regulation of myocardial RLX during ISO-induced myocardial ischemia injury and the protective effect of RLX on ISO-induced cardiac inhibition and fibrosis, which suggests that RLX could be an endogenous cardioprotective factor in ischemic heart diseases.

Animals↗

PubMed2005

Endogenous hydrogen sulfide in patients with COPD.

OBJECTIVES: COPD is characterized by progressive airway obstruction. Recent studies showed that besides nitric oxide (NO) and carbon monoxide (CO), endogenous hydrogen sulfide (H(2)S) might be the third signaling gasotransmitter. To clarify the role of endogenous H(2)S in the pathogenesis of COPD, we investigated the relation of serum H(2)S level to severity of COPD as defined by lung function and airway inflammation. METHODS: Levels of serum H(2)S and NO, lung function, and cell differential counts in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD, and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels measured and underwent Doppler echocardiography. In addition, in order to clarify the effects of age and smoking status on serum H(2)S level, we recruited three groups who were age matched to the study group but had no airflow limitation (59 subjects). RESULTS: Serum H(2)S level (34.0 +/- 0.9 to 36.4 +/- 1.1 micromol/L [+/- SEM]) did not differ among healthy control subjects with different ages (56.6 to 75.0 years, respectively). Serum H(2)S level was significantly higher in patients with stable COPD than in patients with AECOPD and age-matched control subjects (p < 0.01) and correlated positively with NO level in all healthy control subjects and all patients with COPD (r = 0.352, p = 0.000). Serum H(2)S level was significantly lower in smokers than nonsmokers, both with AECOPD (p < 0.05) and healthy control subjects (p < 0.01). It was significantly lower in smokers with AECOPD than healthy smokers and smokers with stable COPD (p < 0.01). Serum H(2)S level differed and was decreased (p < 0.05) among stable COPD patients by stage of airway obstruction (p < 0.05), and it was lower in patients with stage III than stage I obstruction (p < 0.05). Serum H(2)S level in all patients with COPD and healthy control subjects correlated positively with the percentage of predicted FEV(1) value (r = 0.300, p = 0.009). It was lower in patients with AECOPD and systolic pulmonary artery pressure (PASP) > or = 35 mm Hg than those with PASP within the normal range (< 35 mm Hg) [p < 0.05] and was negatively correlated with PASP (r = - 0.561, p = 0.011). Serum H(2)S level was negatively correlated with proportion of neutrophils in sputum (r = - 0.422, p = 0.001) and positively correlated with proportion of lymphocytes (r = 0.286, p = 0.028) and macrophages (r = 0.334, p = 0.01) in all patients with COPD. CONCLUSIONS: Endogenous H(2)S is involved in the pathogenesis of airway obstruction in COPD, and its alteration in level may be connected with disease activity and severity.

Aged↗

PubMed2005

[Changes of the new gaseous transmitter H2S in patients with coronary heart disease].

OBJECTIVE: To investigate the changes of plasma hydrogen sulfide (H(2)S) in patients with coronary heart disease (CHD). METHODS: Plasma H(2)S levels were measured in 40 patients with CHD and 17 angiographically normal patients by sulfide-sensitive electrodes, and the variation of plasma H(2)S levels was analyzed in different clinical types of CHD and in different types of coronary artery lesions. The association of plasma H(2)S levels with the risk factors of CHD was also analyzed. RESULTS: Plasma H(2)S levels were significantly lowered in CHD patients in comparison with that in angiographically normal control subjects (26.10+/-14.27 micromol/L vs 51.74+/-11.94 micromol/L, P<0.001). In CHD patients, plasma H(2)S levels in unstable angina patients (UAP, 23.60+/-14.41 micromol/L) and acute myocardial infarction patients (AMI, 19.98+/-7.516 micromol/L) were significantly lower than that in stable angina patients (SAP, 38.41+/-14.53 micromol/L, P<0.05). No significant difference in plasma H(2)S levels was found between CHD patients with double-vessel and multi-vessel lesions (16.91+/-7.98 vs 18.39+/-7.78 micromol/L, P>0.05), but the two groups of patients had significantly lower plasma H(2)S levels than patients with single-vessel involvement (33.04+/-15.01 micromol/L, P<0.05 and P<0.01, respectively). Plasma H(2)S level was significantly lower in CHD patients with coronary artery occlusion than in patients with simple stenosis (19.04+/-9.55 vs 28.24+/-14.85 micromol/L, P<0.05). Among the CHD patients, H(2)S levels were significantly lower in smokers than in non-smokers (27.54+/-10.37 vs 32.24+/-15.77 micromol/L, P<0.05), also lower in hypertensive patients than in normotensive patients (20.36+/-8.69 vs 33.77+/-15.86 micromol/L, P<0.01). Plasma H(2)S levels showed a significant inverse correlation with blood glucose (r=-0.493 6, P=0.001 6), but there were no significant correlations with sex, age, cholesterol, triglyeride, TC, low-density lipoprotein, high-density lipoprotein, or body mass index. CONCLUSION: Decreased plasma H(2)S levels may correlate with the severity of CHD and changes of the coronary artery, and may implicate the risk factors of CHD such as smoking, hypertension, and high blood glucose.

Adult↗

PubMed2005

[Endogenous hydrogen sulfide in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the role of endogenous hydrogen sulfide (H(2)S) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Levels of serum H(2)S and nitric oxide (NO), lung function and cell differential count in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD and 13 health subjects. Echo-Doppler assessment and arterial blood gas were measured in patients with AECOPD. RESULTS: (1) The serum H(2)S level was significantly higher in patients with stable COPD [(50.8 +/- 2.5) micromol/L] as compared to those in the controls [(39.8 +/- 1.6) micromol/L] and in patients with AECOPD [(33.5 +/- 2.2) micromol/L, P < 0.01]. (2) The level of serum H(2)S was significantly lower in smokers with AECOPD [(28.1 +/- 1.3) micromol/L] as compared to nonsmokers with AECOPD [(39.4 +/- 3.9) micromol/L, P < 0.05] and healthy nonsmokers [(39.8 +/- 1.6) micromol/L, P < 0.01]. (3) There was significant difference in the serum H(2)S level among stable COPD patients with different severity of airway obstruction (P < 0.05); being lower in patients with stage III [(45.1 +/- 4.1) micromol/L] as compared to stage I obstruction [(70.2 +/- 6.2) micromol/L, P < 0.05]. (4) AECOPD with pulmonary hypertension pulmonary artery systolic pressure (PASP) > or = 35 mm Hg (1 mm Hg = 0.133 kPa) showed a lower serum H(2)S level [(26.3 +/- 2.2), (36.2 +/- 2.5) micromol/L, P < 0.05] than that with a normal resting PASP. (5) H(2)S in serum was positively correlated with NO levels (r = 0.278, P = 0.029), FEV(1)% predicted values (r = 0.533, P = 0.000), percentage of sputum lymphocytes (r = 0.286, P = 0.028) and macrophages (r = 0.334, P = 0.01); and negatively correlated with PASP (r = -0.561, P = 0.011) and the percentage of sputum neutrophils (r = -0.422, P = 0.001) in patients with COPD. CONCLUSION: Endogenous H(2)S may be involved in the pathogenesis of airway obstruction in COPD and may be a noninvasive marker of disease activity and severity.

Aged↗

PubMed2004

Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol.

Previous work has shown that the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H(2)S) pathway participates in the regulation of cardiac contraction. We hypothesized that the pathway might participate in the pathophysiological regulation of ischemic heart disease. Isoproterenol injection of rat hearts induced a myocardial ischemic injury model, with reduced myocardial and plasma H(2)S levels, decreased CSE activity, and upregulated CSE gene expression. Exogenous administration of the H(2)S donor NaHS reduced the mortality rate; increased left-ventricular pressure development and left-ventricular-end systolic pressure; and decreased left-ventricular-end diastolic pressure (LVEDP) and subendocardial necrosis, capillary dilatation, leukocytic infiltration, fibroblast swelling, and fibroblastic hyperplasia. As well, production of lipid peroxidation, including myocardial malondialdehyde (MDA), and plasma MDA and conjugated diene, was reduced. Oxidative stress injury is an important mechanism of isoproterenol-induced myocardial injury. In vitro experiments revealed that NaHS might antagonize myocyte MDA production by oxygen-free radicals and that NaHS directly scavenged hydrogen peroxide and superoxide anions. Our results suggest that the endogenous CSE/H(2)S pathway contributes to the pathogenesis of isoproterenol-induced myocardial injury. Administration of exogenous H(2)S effectively protects myocytes and contractile activity, at least by its direct scavenging of oxygen-free radicals and reducing the accumulation of lipid peroxidations.

Alkenes↗

PubMed2004

H2S generated by heart in rat and its effects on cardiac function.

Hydrogen sulfide (H2S), which was considered as a novel gasotransmitter, is produced endogenously from L-cysteine in mammalian brain and vessels, and might be a physiological function regulator to these organs. Here, we showed that mRNA for H2S producing enzyme, cystathionine gamma-lyase, was expressed in myocardial tissues and H2S could endogenously be produced in myocardial tissues. Negative inotropic effect of H2S was proved in present study in vitro and in vivo experiments, and the effect could partly be blocked by glibenclamide, a KATP channel blocker. An intravenous bolus injection of NaHS provoked a decrease in central venous pressure. The present findings suggested that H2S could be endogenously produced by heart tissues, as a physiological cardiac function regulator, mediated by KATP channel pathway.

Animals↗

PubMed2004

Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been reported to have beneficial effects on cardiac function. The authors used the Langendorff model of ischemia/reperfusion (I/R) injury in isolated rat heart to determine whether ghrelin exerts direct cardioprotective effects. Also, the capacity of ghrelin to bind to sarcolemmal membrane fractions before and after ischemia and reperfusion was examined. Compared with vehicle administration, administration of ghrelin (100-10,000 pM) during the reperfusion period resulted in improvement in coronary flow, heart rate, left ventricular systolic pressure, and left ventricular end-diastolic pressure. Ghrelin also enhanced the rates of left ventricular contraction and relaxation after ischemia following reperfusion. Administration of ghrelin during reperfusion reduced myocardial release of lactate dehydrogenase and myoglobin, indicating protection against cardiomyocyte injury. In addition, ghrelin attenuated the depletion of myocardial ATP resulting from ischemia and reperfusion. A receptor-binding assay demonstrated that maximum binding capacity of ghrelin to sarcolemmal membranes was significantly increased after ischemia and was further increased after I/R. However, Scatchard analysis showed that the affinity of ghrelin for its receptor was not altered. The authors have concluded that administration of ghrelin during reperfusion protects against myocardial I/R injury. The cardioprotective effects are independent of growth hormone release and likely involve binding to cardiovascular receptors, a process that is upregulated during I/R.

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