Formaldehyde induced the cardiac damage by regulating the NO/cGMP signaling pathway and L-Ca2+ channels.

Background: Formaldehyde (FA) is a common environmental pollutant that has been found to cause negative cardiovascular effects, however, the toxicological mechanism is not well understood. In this study, we investigated the molecular effects of the Nitric Oxide (NO)/cyclic Guanosine Monophosphate (cGMP) signaling pathway and L-type calcium (L-Ca2+) channels in rat hearts. Methods: We designed the short-term FA exposure on the rat heart in different concentrations (0, 0.5, 3, 18 mg/m3). After 7 days of exposure, the rats were sacrificed and the rat tissues were removed for various experiments. Results: Our experimental data showed that FA resulted in the upregulation NO and cGMP, especially at 18 mg/m3. Further, when exposed to high concentrations of FA, Cav1.2 and Cav1.3 expression decreased. We conclude that the NO/cGMP signaling pathway and downstream related channels can be regulated by increasing the production of NO in the low concentration group of FA. High concentration FA directly regulates L-Ca22+ channels. Conclusion: This study suggests that FA damages the function of the cardiovascular system by regulating the NO/cGMP signaling pathway and L-Ca2+ channels.

Changes of heavy metal concentrations in farmland soils affected by non-ferrous metal smelting in China: A meta-analysis.

Long-term human smelting activities have resulted in substantial heavy metals (HMs) pollution of farmland soils around smelting sites, and the safety of farmland products is critical for human health. The current study focuses on HMs in farmland soils surrounding a single smelter, therefore the impact of smelting on a national scale needs to be investigated further. This study was based on 116 papers and 1143 sets of relevant data for meta-analysis, and a hierarchical mixed-effects model was used to quantify the changes of HMs concentrations in farmland soils affected by non-ferrous metal smelting on a national scale, as well as their relationships with relevant explanatory variables in China. Results showed that: (i) non-ferrous metal smelting substantially increased farmland soils HMs concentrations (323%), with each HM concentration increasing in the following order: Cd (2753%) > Pb (562%) > Hg (455%) > Zn (228%) > Cu (158%) > As (107%) > Ni (52%); (ii) the highest increase of HMs in vegetable fields (361%), but not significant in comparison to other farmland categories, and the increase of Pb, Zn, Cu and As concentrations were significantly different in different types of smelting areas; (iii) the increase of Hg was significantly higher in the northern region than in the southern region, and the opposite increase of Cu; (iv) the soil depth from 0 to 40 cm was significantly affected by smelting, and the increase of multiple HMs were significantly positively correlated with soil pH and negatively correlated with distance; (v) the other explanatory variables (farmland category and soil organic matter) were not significantly related to the effect of smelting. The results can provide some reference for protecting and restoring farmland soils around smelting areas.

Characteristics and Risk Assessment of PAH Pollution in Soil of a Retired Coking Wastewater Treatment Plant in Taiyuan, Northern China.

We analyzed the soil at the site of a former coking wastewater treatment plant on redeveloped land in Taiyuan, northern China, in an attempt to detect the presence of 16 types of priority polycyclic aromatic hydrocarbons (PAHs) listed by the United States Environmental Protection Agency (US EPA) and evaluate the potential pollution risks. The results show that the total proportion of PAHs in the surface soil of the redeveloped land ranged from 0.3 to 1092.57 mg/kg, with an average value of 218.5 mg/kg, mainly consisting of high-ring (5-6 rings) components. Characteristic ratio analysis indicated that the pollution was mainly related to the combustion of petroleum, coal, and biomasses. The wastewater treatment units operated according to the following treatment train: advection oil separation tank, dissolved air flotation tank, aerobic tank, secondary sedimentation tank, and sludge concentration tank. Our study found that pollution resulting from low-ring PAHs mainly appeared in the advection oil separation tank during the pre-wastewater treatment stage, while medium-ring PAH contamination mainly occurred in the dissolved air floatation tank, aerobic tank, and secondary sedimentation tank during the middle stages of wastewater treatment. High-ring PAH contamination primarily appeared in the sludge concentration tank in the latter stage of wastewater treatment. Based on our assessment of the ecological risk using the Nemerow Comprehensive Pollution Index and the toxicity equivalent factor (TEF) method, we determined that individual PAHs in the study area exceeded acceptable levels and the total amount of pollution was potentially harmful to the ecological environment. In addition, the comprehensive lifetime cancer risk for different populations resulting from exposure to the soil in the study area was determined to be within acceptable limits based on the average PAH concentrations.

Response of Chinese pine regeneration density to forest gap and slope aspect in northern China: A meta-analysis.

Chinese pine is a Chinese endemic species with important ecological functions. Forest gaps and slope aspect are important factors in the regeneration of Chinese pine by influencing light and moisture, but what these effects are is still up for debate. Meanwhile, the effects of forest gaps and slope aspect are poorly studied in response to different forest types and ages, as well as temperature and precipitation. We established literature selection criteria that finally identified 101 and 69 pairs of study cases on forest gaps and slope aspect, respectively. The overall effect values were obtained by meta-analysis and found that gap and shady slope habitats had significant positive effects on the regeneration density of Chinese pine (P < 0.05). The gap most enhanced the regeneration density in a plantation setting (P < 0.05). In pure stands of Chinese pine, shady slopes can significantly increase regeneration density (P < 0.05). Forest gaps and shady slopes contributed most to Chinese pine regeneration density in mature stands compared to near mature stands, and over mature stands (P < 0.05). There was no significant effect of stand gap size on regeneration density (P > 0.05). In particular, the edges of the gap appeared to be well-suited for regeneration (P < 0.05). In our study area, mean annual precipitation resulted in a significant increase in the effects of the gap and shady slope as precipitation declined (P < 0.05). This meta-analysis helps elucidate the effects of forest gap (position or area) and slope aspect on Chinese pine regeneration. With global climate change, Chinese pine regeneration may prefer the edge of forest gaps and shady slopes.

Vacancy-Modulated of CuS for Highly Antibacterial Efficiency via Photothermal/Photodynamic Synergetic Therapy.

Cu-based nanomaterials have been developed to alleviate the problem of antibiotic resistance due to their superior properties and good biocompatibility. Defects in nanomaterials have a major role in improving photocatalytic performance. Herein, two CuS nanospheres with predominant VCuSCu and VCuSS vacancy (abbreviated as CuS and CuS-T150, respectively) characterized by positron annihilation spectra are synthesized. The combination of experimental and theoretical calculation results demonstrates that CuS-T150 exhibits excellent antibacterial, achieving bactericidal rates of 99.9% against to Escherichia coli (E. coli) under 808 nm laser irradiation. Compared with CuS, the superior antimicrobial activity of CuS-T150 is mainly attributed to its stronger ability to adsorb oxygen molecules, more easily bind with surface of E. coli, and higher photothermal conversion efficiency (PTCE). This work provides a deeper understanding of nanomaterials with vacancy modulated the antibacterial efficiency by synergistic effect of photodynamic and photothermal therapy.

Effect of hydrogen sulfide on glycolysis-based energy production in mouse erythrocytes.

Hydrogen sulfide (H2 S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2 S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2 S on glycolysis-mediated energy production. The purpose of this study was to determine the effect of H2 S on glycolysis-mediated energy production in mitochondria-free mouse RBCs. Western blot analysis showed that the only H2 S-generating enzyme expressed in mouse RBCs is 3-mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2 S. Both exogenously administered H2 S salt and MST-derived endogenous H2 S stimulated glycolysis-mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2 S levels and MST activity in mouse RBCs. The mitochondria-targeted H2 S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3-100 µM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300-1000 µM) lowered ATP levels, but prolonged cell viability. H2 S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen-independent energy production.

Disturbance of di-(2-ethylhexyl) phthalate in hepatic lipid metabolism in rats fed with high fat diet.

Di-(2-ethylhexyl) phthalate (DEHP), which is widely used as an industrial plasticizer, may cause liver damage. Concomitantly, bad dietary habits can exacerbate the liver burden. In this study, high-fat diet (HFD)-fed rats were treated with DEHP (10, 100, or 300 mg/kg bw) for 5 weeks, and a biochemical method was adopted to detect serum lipid contents. Key metabolic genes and pathological changes were assessed by different methods (RT-PCR, Western Bloting, ELISA and HE staining). The rats which were exposed to DEHP at a dose of 10 mg/kg bw exhibited dyslipidemia and increased transcription of SREBP-1 and its target FAS, thereby prompting de novo lipogenesis, but they did not become obese. Instead, DEHP at a dose of 300 mg/kg bw elevated the levels of AMPK phosphorylation and the mRNA levels of PPAR-α, PGC-1α, CPT-1 and lipin-1 in the liver, which led to fatty acid oxidation. Additionally, DEHP at the highest dose increased the TNF-α mRNA expression in the liver. Based on these findings, we conclude that excess fatty acid oxidation might increase the inflammatory response. No toxic effects on hepatic function were observed. These findings suggest that different doses of DEHP have the potential to disturb hepatic metabolic imbalance in HFD-fed rats.

H2S-stimulated bioenergetics in chicken erythrocytes and the underlying mechanism.

The production of H2S and its effect on bioenergetics in mammalian cells may be evolutionarily preserved. Erythrocytes of birds, but not those of mammals, have a nucleus and mitochondria. In the present study, we report the endogenous production of H2S in chicken erythrocytes, which was mainly catalyzed by 3-mercaptopyruvate sulfur transferase (MST). ATP content of erythrocytes was increased by MST-generated endogenous H2S under normoxic, but not hypoxic, conditions. NaHS, a H2S salt, increased ATP content under normoxic, but not hypoxic, conditions. ATP contents in the absence or presence of NaHS were eliminated by different inhibitors for mitochondrial electron transport chain in chicken erythrocytes. Succinate and glutamine, but not glucose, increased ATP content. NaHS treatment similarly increased ATP content in the presence of glucose, glutamine, or succinate, respectively. Furthermore, the expression and activity of sulfide:quinone oxidoreductase were enhanced by NaHS. The structural integrity of chicken erythrocytes was largely maintained during 2-wk NaHS treatment in vitro, whereas most of the erythrocytes without NaHS treatment were lysed. In conclusion, H2S may regulate cellular bioenergetics as well as cell survival of chicken erythrocytes, in which the functionality of the electron transport chain is involved. H2S may have different regulatory roles and mechanisms in bioenergetics of mammalian and bird cells.

Investigating the inotropic effect of pyruvic acid on the isolated rat heart and its underlying mechanism.

Pyruvic acid is important organic chemical intermediates that plays a role in cardiomyocyte pathophysiology and therapy. This study sought to explore the inotropic effects of pyruvic acid on the function of the isolated rat hearts and investigate its underlying mechanism. Pyruvic acid produced a greater negative inotropic effect compared to HCl and sodium pyruvate in a concentration-dependent pattern in the hearts. The role of low dose of pyruvic acid on heart function was regulated by pyruvic acid molecules and high dose pyruvic acid may be influenced by pyruvic acid molecules and pH. Kv channels may be involved in the pyruvic acid-induced negative inotropic effect. Finally, pyruvic acid markedly increased the level of LDH and CK and reduced the level of Ca2+Mg2+-ATPase and Na+K+-ATPase. These results suggest that pyruvic acid may modulate cardiac function at physiological or low doses but can cause damage to cardiomyocytes at high doses.

Formic acid up-regulates vascular tension through nitric oxide-cGMP signaling pathway.

Formic acid is a common organic acid used in many industrial processes. There is a paucity of research on the direct toxicity of formic acid and how it might affect the cardiovascular system. This study aimed to understand the effect of formic acid on vascular tension in an animal model and the underlying mechanism. Results found that the vasodilation induced by formic acid was related to the endothelium. When the dosage of formic acid was 1 mM or 5 mM, the vasodilation of endothelium-intact rings was partially suppressed by l-NAME, NS-2028 and nifedipine, and vasoconstriction caused by CaCl2 was inhibited, and the mRNA levels of eNOS, the activity of NOS (tNOS, iNOS and cNOS) and the level of NO and cGMP were significantly increased. Results also found that eNOS protein expression was significantly enhanced by 5 mM of formic acid. These results suggest formic acid can relax the aortic vessels of rats in a dose-dependent pattern. Further, the mechanism of the formic acid-induced vasodilatation likely involved the NO/cGMP pathway. Finally, the current study has revealed that vasodilation induced by high concentrations of formaldehyde may be the effect of the metabolite formic acid. This study will help further inform the etiologies of formic acid-related angiocardiopathies.

Formaldehyde regulates vascular tensions through nitric oxide-cGMP signaling pathway and ion channels.

Formaldehyde (FA) has been linked to the detrimental cardiovascular effects. Here, we explored the effects and mechanisms of FA on rat aortas both in vivo and in vitro. The results presented that FA evidently lowered the blood pressures of rats. The expression levels of BKCa subunits α and ß1 and iNOS of the aortas were up-regulated by FA in vivo. However, FA markedly reduced the levels of Cav1.2 and Cav1.3, which are the subunits of L-Ca2+ channel. Furthermore, the contents of NO, cGMP and iNOS in the aortas were augmented by FA. To further confirm these findings, the mechanisms accredited to these effects were examined in vitro. The data showed that FA contracted the isolated aortic rings at low concentrations (<300 µM), while it relaxed the rings at high concentrations (>500 µM). The FA-induced vasoconstriction at low concentrations was blocked partly by an inhibitor of ACE. The relaxation caused by FA at high concentrations was attenuated by the inhibitors of NO-cGMP pathway, L-Ca2+ channel and BKCa channel, respectively. Similarly, the expression of iNOS was strongly enhanced by FA in vitro. The effects of FA on the aortic rings with endothelium were significantly greater than those on the rings without endothelium. Our results indicate that the vasoconstriction of FA at low concentrations might be partially pertinent to endothelin, and the FA-caused vasorelaxation at high concentrations is possibly associated with the NO-cGMP pathway, L-Ca2+ channel and BKCa channel. This study will improve our understanding of the pathogenic mechanisms for FA-related cardiovascular diseases.

The molecular mechanisms of sodium metabisulfite on the expression of K ATP and L-Ca2+ channels in rat hearts.

Sodium metabisulfite (SMB) is used as an antioxidant and antimicrobial agent in a variety of drugs and foods. However, there are few reported studies about its side effects. This study is to investigate the SMB effects on the expression of ATP-sensitive K(+) (KATP) and L-type calcium (L-Ca(2+)) channels in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A were increased by SMB; on the contrary, SMB at 520 mg/kg significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SMB can activate the expression of KATP channel by increasing the mRNA and protein levels of Kir6.2 and SUR2A, while it inhibits the expression of L-Ca(2+) channels by decreasing the mRNA and protein levels of Cav1.2 and Cav1.3 in rat hearts. Therefore, the molecular mechanism of the SMB effect on rat hearts might be related to the increased expression of KATP channels and the decreased expression of L-Ca(2+) channels.

Effect of sulfur dioxide inhalation on the expression of KATP and L-Ca(2+) channels in rat hearts.

Epidemiological studies have revealed an association between sulfur dioxide (SO2) exposure and cardiovascular diseases. This study is designed to investigate the SO2 effect on the expression of ATP-sensitive K(+) (KATP) channel and L-type calcium (L-Ca(2+)) channel in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A of rat hearts in SO2 groups were higher than those in control group. SO2 at 14mg/m(3) significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SO2 can activate the KATP channels by up-regulating the expression of Kir6.2 and SUR2A, while it inhibits the L-Ca(2+) channels by down-regulating the expression of Cav1.2 and Cav1.3 in rat hearts. The molecular mechanism of SO2-induced negative inotropic effect might be linked to the expression changes of these subunits, which may contribute to the pathogenesis of SO2-associated cardiovascular diseases.

Effects of coarse chalk dust particles (2.5-10 µm) on respiratory burst and oxidative stress in alveolar macrophages.

The main aim of the present study was to examine in vitro responses of rat alveolar macrophages (AMs) exposed to coarse chalk dust particles (particulate matter in the size range 2.5-10 µm, PM(coarse)) by respiratory burst and oxidative stress. Chalk PM(coarse)-induced respiratory burst in AMs was measured by using a luminol-dependent chemiluminescence (CL) method. Also, the cell viability; lactate dehydrogenase (LDH) release; levels of cellular superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and acid phosphatase (ACP); plasma membrane ATPase; and extracellular nitric oxide (NO) level were determined 4 h following the treatment with the different dosages of chalk PM(coarse). The results showed that chalk PM(coarse) initiated the respiratory burst of AMs as indicated by strong CL, which was inhibited by diphenyleneiodonium chloride and L-N-nitro-L-arginine methyl ester hydrochloride. It suggested that chalk PM(coarse) induced the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in AMs. This hypothesis was confirmed by the fact that chalk PM(coarse) resulted in a significant decrease of intracellular SOD, GSH, ACP, and ATPase levels and a notable increase of intracellular CAT, MDA content, and extracellular NO level, consequently leading to a decrease of the cell viability and a increase of LDH release. It was concluded that AMs exposed to chalk PM(coarse) can suffer from cytotoxicity which may be mediated by generation of excessive ROS/RNS. Graphical Abstract The possible mechanism of coarse chalk particles-induced adverse effects in AMs.

Effects of sodium metabisulfite on the expression of BK(Ca), K(ATP), and L-Ca(2+) channels in rat aortas in vivo and in vitro.

Sodium metabisulfite (SMB) is most commonly used as the preservative in many food preparations and drugs. So far, few studies about its negative effects were reported. The purpose of this study was to investigate the effect of SMB on the expression of big-conductance Ca(2+)-activated K(+) (BKCa), ATP-sensitive K(+) (KATP), and L-type calcium (L-Ca(2+)) channels in rat aorta in vivo and in vitro. The results showed that the mRNA and protein levels of the BKCa channel subunits α and ß1 of aorta in rats were increased by SMB in vivo and in vitro. Similarly, the expression of the KATP channel subunits Kir6.1, Kir6.2, and SUR2B were increased by SMB. However, SMB at the highest concentration significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. These results suggest that SMB can activate BKCa and KATP channels by increasing the expression of α, ß1, and Kir6.1, Kir6.2, SUR2B respectively, while also inhibit L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of aorta in rats. The molecular mechanism of SMB-induced vasorelaxant effect might be related to the expression changes of BKCa, KATP, and L-Ca(2+) channels subunits. Further work is needed to determine the relative contribution of each channel in SMB-mediated vasorelaxant effect.

Effects of gaseous sulfur dioxide and its derivatives on the expression of KATP, BKCa and L-Ca(2+) channels in rat aortas in vitro.

Epidemiological investigations have revealed that sulfur dioxide (SO2) exposure is linked to cardiovascular diseases. Our previous study indicated that the vasorelaxant effect of SO2 might be partly related to ATP-sensitive K(+) (KATP), big-conductance Ca(2+)-activated K(+) (BKCa) and L-type calcium (L-Ca(2+)) channels. The present study was designed to further investigate the effects of gaseous SO2 and its derivatives on the gene and protein expression of these channels in the rat aortas in vitro. The results showed that the mRNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2 and SUR2B of the rat aortas in SO2 and its derivatives groups were higher than those in control group. Similarly, the expression of the BKCa channel subunits α and ß1 was increased by SO2 and its derivatives. However, SO2 and its derivatives at 1500µM significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. Histological examination of the rat aorta tissues showed moderate injury of tunica media induced by SO2 and its derivatives at 1500µM. These results suggest that SO2 and its derivatives can activate the KATP and BKCa channels by increasing the expression of Kir6.1, Kir6.2, SUR2B and α, ß1, respectively, while also inhibiting the L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of the rat aortas. The molecular mechanism of the vasorelaxant effect of SO2 and its derivatives might be related to the expression changes of KATP, BKCa and L-Ca(2+) channel subunits, which may play a role in the pathogenesis of SO2-associated cardiovascular diseases.

The vasorelaxant effect and its mechanisms of sodium bisulfite as a sulfur dioxide donor.

To study the biological role of bisulfite on vascular contractility and its underlying cellular and molecular mechanisms, to explore whether bisulfite can be used as a sulfur dioxide (SO(2)) donor in the biological experiments, the vasorelaxant effects of sodium bisulfite and sodium sulfite on isolated rat thoracic aortic rings were compared; and the signal transduction pathways and the ion channels involved in the vascular effects of bisulfite were investigated. The results show that: (1) Sodium bisulfite relaxed rat thoracic aortic rings in a concentration-dependent manner (from 100 to 4000 µM); however, sodium sulfite at 500 and 1000 µM caused vasoconstriction, and only at higher concentrations (from 2000 to 4000 µM) it caused vasorelaxation in a concentration-dependent manner. (2) The vasorelaxation caused by the bisulfite at low concentrations (≤500 µM) was endothelium-dependent, but at high concentrations (≥1000 µM) it was endothelium-independent. (3) The vasorelaxation by the bisulfite at the low concentrations was partially mediated by the cGMP pathway and the vasorelaxation was related to big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, but not due to prostaglandin, protein kinase C (PKC) and cAMP pathways. (4) The vasorelaxation by the bisulfite at high concentrations was partially inhibited by tetraethylammonium (TEA) and glibenclamide, suggesting that the vasorelaxation was related to ATP-sensitive K(+) channel (K(ATP)) and L-type calcium-channel. These results led to the conclusion that bisulfite (HSO(3)(-)) might be a vasoactive factor and sodium bisulfite can be used as a SO(2) donor for the study of SO(2) biology.

The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart.

Epidemiological investigations have revealed that sulfur dioxide (SO(2) ) exposure is linked to cardiovascular diseases. The present study was designed to investigate the negative inotropic effects of gaseous SO(2) and its derivatives in the isolated perfused rat heart and the possible mechanisms involved in their effects. The results showed that both SO(2) and SO(2) derivatives elicited a negative inotropic effect in a dose-dependent manner, and SO(2) produced a higher negative effect than SO(2) derivatives. The mechanism of SO(2) -induced negative inotropic effects at low concentrations was different from that at high concentrations. At low concentrations, the mechanism of SO(2) -induced negative inotropic effects might occur through promoting the activities of protein kinase C (PKC), cycloxygenase, and cGMP, while the mechanism of SO(2) derivatives-induced effects might be related to the opening of ATP-sensitive K(+) (K(ATP) ) channel and the inhibition of Ca(2+) influx via L-type calcium-channel. At high concentrations, the mechanisms of SO(2) and SO(2) derivatives-induced negative inotropic effects were similar, which might be related to the K(ATP) channel and L-type calcium-channel as well as the possible alterations in PKC, cycloxygenase, and cGMP. Further work is needed to determine the relative contribution of each pathway in SO(2) -mediated inotropic effect.

The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved.

Ammonia (NH(3)) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH(3) in the nervous system have been studied. Recently, endogenous NH(3) has been suggested to be a gas transmitter. However, so far the role of NH(3) in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH(3) on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH(3) had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH(4)Cl. At low concentrations, the effect of NH(3) on cardiac function was caused by NH(3) molecules; at high concentrations, the effect of NH(3) on hearts may be partly correlated with a change of pH value, but was mainly caused by NH(3) molecules. The mechanisms involved in the NH(3)-induced positive inotropic effect may be related to the ATP-sensitive K(+) (K(ATP)) channel and the nitric oxide (NO)-cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l(-1), NH(3) significantly increased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary perfusate and decreased the activity of Na(+),K(+)-ATPase and Ca(2+),Mg(2+)-ATPase in the hearts. These results indicate that NH(3) at physiological or low concentrations may play a modulatory role in heart function, but at high concentrations had a damaging effect on isolated rat hearts.

Vasodilator effect of gaseous sulfur dioxide and regulation of its level by Ach in rat vascular tissues.

To explore the toxicological and physiological role of gaseous SO(2) on vascular contractility and its level in vascular tissues, a vasodilation study of isolated rat thoracic aortic rings by gaseous SO(2) was carried out. The level of SO(2) in vascular tissue was assayed using a modified high-performance liquid chromatographic method with fluorescence detection (HPLC-FD). The results show that gaseous SO(2) (from 1 microM to 2000 microM) relaxed rat thoracic aortic rings in a dose-dependent manner. The physiological concentrations of SO(2) in thoracic aortic tissues and plasma in rats were 127.76 +/- 31.34 microM and 16.77+/-8.24 microM, respectively; The vasorelaxant effect of gaseous SO(2) at physiological and low concentrations (<450 microM) was endothelium dependent, and at high concentrations (>500 microM) was endothelium independent. The results also show that SO(2) could be endogenously generated in vascular tissues, and mainly in vascular endothelial cells; acetylcholine (Ach) increased the SO(2) level in vascular tissue, and noradrenaline (NE) decreased the SO(2) level. These findings demonstrate that gaseous SO(2) is a vasorelaxant substance, and the vasorelaxant effect of gaseous SO(2) is much stronger than that of its derivatives sulfite and bisulfite, which result from the inactivation process of SO(2) gas transmitter by which SO(2) is hydrated to form sulfite, and the latter is enzymatically oxidized to form sulfate. These findings also demonstrate that endogenous SO(2) level in vascular tissue may be regulated by Ach and NE.