Objective: To explore the role and the possible mechanism of hydrogen sulfide (H 2S) in modulating the remodeling of aorta of hypertensive rats. Methods: Twenty-four male WKY rats were randomly divided into WKY control group, WKY+ NaHS (H 2S donor) group and WKY+PPG group. Another twenty-four male SHR rats at the age of 4 weeks were also divided into SHR control group, SHR+NaHS group and SHR+PPG group. SHR control and WKY control rats were injected with water, rats of SHR+NaHS group and WKY+ NaHS group were injected with NaHS, rats of SHR +PPG group and WKY +PPG group were injected with PPG each day. Five weeks later, the blood pressure was determined. The rat aortas were dyed with Weigert’s Method. The morphometric parameters including outer radius, lumen radius and the media area were calculated by Leica workstation. The proliferation of smooth muscle cells was detected by immunohistochemical assay of PCNA. Results: The morphometric parameters of outer radius, lumen radius, medium area, and the ratio of wall thickness to lumen radius in SHR control rats were all higher than those of WKY control rats [outer radius (1 999?45) ?m vs (1 790? 96) ?m, lumen radius(1 759?91) ?m vs (1 636?94) ?m, medium area (0.60?0.06) ?m 2 vs (0.48? 0.03) ?m 2, and the ratio of wall thickness to lumen radius (0.066?0.006) vs (0.060? 0.004)]. Expression of PCNA in aorta of SHR control rats was higher than that of WKY con-trol rats too. Most of the structural remodeling parameters decreased in the rats of SHR+NaHS group [outer radius(1 864?66) ?m, lumen radius (1 634?66) ?m, medium area (0.53?0.06) ?m 2] compared with those in rats of SHR control group. Expression of PCNA in aorta of SHR+NaHS control rats decreased compared with that of SHR control rats at the same time. Conclusion: H 2S is one of the key factors playing important roles in the modulation of the structural remodeling in aorta of SHR rats. Exogenous administration of H 2S may attenuate the development of hypertensive rat aorta remodeling effectively.

Sulfur dioxide (SO_2) is an ordinary air pollutant globally and harm to human health. L-cysteine is the major sulfur-containing amino acid and its normal metabolism can produce hydrogen sulfur (H_2S) and SO_2. It is realized that H_2S has various bioactivities and is the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO). Recently, attention has been paid to the physiologic effects of endogenous SO_2 and its derivatives (bisulfite and sulfite) in vivo, and recognized that SO_2 and its derivatives can lower blood pressure, change heart rates, participate in inflammatory reactions, and so on, suggesting that endogenous SO_2 may modulate the physiologic functions in vivo as a bioactive molecule.

Objective: To study the effects of adrenomedullin (ADM) and proadrenomedullin N terminal 20 peptide (PAMP) alone or in combinations on the isolated rat hearts as well as the possible signaling pathways involved in their actions. Methods: In isolated rat hearts, the left ventricular pressure (LVP), LVP?dp/dtmax, coronary fluid (CF) and heart rate(HR) of the hearts infused at different concentrations of ADM and/or PAMP were determined by a 4 cannal physiological recorder, then the cAMP contents were assayed in myocardium. Results: After being infused with ADM from 10 -11 to 10 -8 mol?L -1 or PAMP from 10 -11 to 10 -8 mol?L -1 , the LVP and LVP?dp/dtmax of the isolated hearts decreased gradually in a concentration dependent manner, and at the same concentration, the effects of PAMP were more potent than those of the ADM. When ADM and PAMP were co administrated with both concentrations as low as from 10 -11 to 10 -10 mol?L -1 , the cardiac parameters were decreased more than either ADM or PAMP administrated alone. However, the inhibitory effects of ADM and PAMP were attenuated when they were in combination at higher concentrations as from 10 -9 to 10 -8 mol?L -1 . When the rat hearts were infused with ADM, PAMP,and ADM plus PAMP, the CF were always higher than those of the controls and decreased when co administrated with L NAME, an inhibitor of NOS, but the decreaseddegree of LVP and LVP?dp/dtmax were attenuated by L NAME.The cAMP contents in the left cardiac ventricle were increased significantly by ADM infusions but not changed obviously by PAMP, and were of no statistical difference in rat hearts with ADM administrated alone from those combinated with ADM and PAMP. Conclusion: These results showed that ADM and PAMP infused alone or in combinations inhibited the function of rat hearts in vitro, which might be partly involved with the NOS/NO pathway.

Objective:To constract a method of measurement microamount hydrogen sulfide (H_2S) using sensitive sulphur electrode. Methods: According to the physical and chemical characters of H_2S, H_2S, 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_2S was converted, a method was constructed to measure the H_2S. It was used to analyze the concentrations of H_2S of plasma in rats and humans, the endogenous concentration of H_2S 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 ?mol/L was found using sensitive sulphur electrod. The H_2S levels of plasma in male and female rats were 40?4 and 41?5 ?mol/L, respectively, and significant difference was not found; those in venous blood plasma of men and women were 33?4 ?mol/L and 35?5 ?mol/L respectively, without significant difference. There were not significant differences in the aortic endogenous levels of H_2S (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_2S pathway in cardiovascular research.

AIM: To investigate the activity and distribution of calcineurin (CaN) in different tissues of rat. METHODS: Using western blot and immunohistochemical staining methods to measure the amount and location of CnA?, isoform of catalytic subunit of CaN in different tissues of rat. CaN activity was measured by labelled substrate peptide. RESULTS: 1. Western blot showed that CnA? expression was detected in brain, heart, skeletal muscle and lung tissues. There was no detectable CnA? expression in kidney and aorta. 2. In immunohistochemical staining study, there was strong immunostaining of CnA? in brain. CnA? was located in cytoplasm of cardiac cell, macrophage and connective tissue of peribronchiolar in lung tissue, aorta adventitia, connective tissue around small vessels and outer wall of renal tube. 3. CaN activity was highest in brain, the following was skeletal muscle, myocardium and lung tissue. CaN activity was lowest in aorta and kidney tissue. CONCLUSION: CaN is widely distributed in rats and might be involved in functional regulation of various organs and tissues.

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.

AIM: To explore the mechanism of apoptosis in pulmonary arterial vascular smooth muscle cells (PASMCs) induced by nitric oxide (NO). METHODS: Wistar rat PASMCs were isolated from explants from the intrapulmonary, incubated with NO donor, sodium nitroprussid (SNP) under 12 or 24 hour normoxic and hypoxic conditions. The cell cycle progression and sub-G 1 of PASMC were analyzed via flow cytometric staining of propidium iodide, and the expression of nuclear transcription factor NF-?B and pro-apoptotic factors caspase-3 were detected using immunochemistry staining. Meanwhile gel electrophoresis of extracted DNA by PASMC was performed. RESULTS: SNP induced PASMC apoptosis in a dose-dependent manner ( P

AIM: To explore the effects of hydrogen sulfide (H_2S) on proliferation of vascular smooth muscle cells (VSMC) stimulated by endothelin (ET-1, 10 -7 mol/L ) and mitrogen-activated protein kinase (MAPK) activity in VSMCs. METHODS: Cultured VSMCs were divided into six groups: (1) control group, (2) serum group, (3) endothelin group, (4) NaHS groups, (5) serum+NaHS group, and (6) endothelin+NaHS group. VSMC proliferation was measured by [ 3H]-TdR incorporation and MAPK activity in VSMC was determined by radioactivity assay. RESULTS: ET-1 increased VSMC [ 3H]-TdR incorporation by 2.39 times ( P

AIM AND METHODS: To explore the effects calcitonin gene-related peptide (CGRP) and endothelin-1(ET-1) on the mechanisms of hypoxic pulmonary hypertension (HPH),the contents of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in extractives of lung and ventricular tissues of the chronic hypoxic rats were determined by radioimmunoassay. The changes of their hemodynamic indices and right heart hypertrophy index were monitored simultaneously. RESULTS: The level of pulmonary artery plasma CGRP was significantly higher than that of thoracic aorta plasma,but just the reverse was ET-1 or the ratio of ET-1 and CGRP in control rats( P

AIM: The activity and expression of neutral endopeptidase (NEP) and the adrenomedullin (ADM) contents in various tissues were observed in septic shock and control rats to study the possible role of NEP in the change of ADM contents in tissues during septic shock. METHODS: The septic shock model of rats were established by cecal ligation and puncture (CLP). ADM contents, NEP activities, level of NEP mRNA and NEP protein were measured. RESULTS: (1) In early septic shock (ES), the ADM contents were generally higher in detected tissues, the NEP activity in left ventricle and small intestine were lower and was higher in blood than those in controls, and in lung, kidney and aorta were similar with the controls. NEP immunoreactive staining were less in lung, left ventricle, endothelium and media of aorta, but more in adventitia of aorta and kidney than those of the controls; (2) In late septic shock (LS), the ADM contents in small intestine was less but in plasma and other tissues were higher, and the NEP activity were less in plasma and other tissues than those in ES. The NEP immunoreactive staining were less in heart, endothelium and media of aorta, lung and kidney than those in ES, and was no significant change in adventitia of aorta compared with those of ES. RT-PCR found that NEP gene expression were significantly less in left ventricle, aortas, lung and small intestine than those in the controls. CONCLUSIONS: In septic shock rats, the NEP activity changes heterogeneously but the ADM contents elevate in most tissues. These results indicate that during the septic shock, the local concentrations and actions of ADM in various tissues may be regulated differently by the NEP. [