The contractile and diastolic function of smooth muscle cells (SMCs) is closely related to penile erection and erectile dysfunction (ED). In addition to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), sulfur dioxide (SO2), estrogen receptor (ER), P2Y receptor, perivascular tissue (PVT), and calcium activated potassium channel (Kca) are found to be involved in the relaxation of SMCs. This review updates the mechanisms of the relaxation of SMCs and its relationship with ED.
Carbon Monoxide ; physiology ; Erectile Dysfunction ; etiology ; physiopathology ; Humans ; Hydrogen Sulfide ; metabolism ; Male ; Muscle Contraction ; Muscle, Smooth ; Myocytes, Smooth Muscle ; physiology ; Nitric Oxide ; physiology ; Penile Erection ; physiology ; Potassium Channels, Calcium-Activated ; physiology ; Receptors, Estrogen ; physiology ; Receptors, Purinergic P2Y ; physiology ; Sulfur Dioxide ; metabolism

OBJECTIVETo investigate the protective effect of high-pressure carbon monoxide for preservation of ex vivo rabbit heart graft in comparison with the conventional HTK cardioplegic solution preservation.

METHODSHeart grafts isolated from 85 New Zealand rabbits were randomly divided into Naive group (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8, 10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for 30 min with a modified Langendorff apparatus and examined for left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia score (AS), myocardial ultrestructure, and cardiac enzyme profiles.

RESULTSAfter preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and diastolic functions were significantly better in CO group than in HTK group, but these differences were not obvious between the two groups after graft preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures occurred in the isolated hearts after a 24-h preservation in both CO and HTK groups, but the myocardial damages were milder in CO group.

CONCLUSIONPreservation using high-pressure carbon monoxide can better protect isolated rabbit heart graft than the conventional HTK preservation approach especially for prolonged graft preservation.

Animals ; Carbon Monoxide ; Cardioplegic Solutions ; Glucose ; Heart ; physiology ; Heart Transplantation ; Myocardium ; ultrastructure ; Rabbits ; Tissue Preservation ; methods ; Tromethamine

OBJECTIVETo investigate the role of heme oxygenase and carbon monoxide (HO/CO) in the development of spontaneous pain and hyperalgesia of rats induced by formalin injection.

METHODSZinc protoporphyrin Znpp (the inhibitor of HO) was intrathecally injected to the rats with formalin inflammatory pain. Hemin (the agonist of HO) was intrathecally injected to the normal rats. The weighted pain scores were used to evaluate the degree of pain response. Thermal withdrawal latency and mechanical withdrawal threshold were observed to assess the degree of thermal hyperalgesia and mechanical allodynia.

RESULTSAfter the intrathecal injection of Znpp, the weighted pain score obviously reduced in a dose-dependent manner compared with the rats with formalin inflammatory pain. Intrathecal injection of Znpp had no obvious effect on thermal withdrawal latency and mechanical withdrawal threshold in injected feet compared with formalin group. But there was a prolongation in a dose-dependent manner in non injected feet. Intrathecal injection of Hemin to normal rats could shorten the thermal withdrawal latency and reduce the mechanical withdrawal threshold on both sides of hindpaws.

CONCLUSIONIntrathecal injection of the HO inhibitor produced prominent inhibition to pain related behavior and thermal and mechanical hyperalgesia induced by formalin injection. Intrathecal injection of HO inductor could induce thermal and mechanical hyperalgesia in normal rats. The results indicated that HO/CO took part in the processes of spinal cord nociceptive information transmission and the development of thermal and mechanical hyperalgesia.

Animals ; Carbon Monoxide ; Formaldehyde ; adverse effects ; Heme Oxygenase (Decyclizing) ; antagonists & inhibitors ; Hemin ; Hyperalgesia ; chemically induced ; Male ; Nociception ; Nociceptors ; drug effects ; physiology ; Pain ; chemically induced ; Protoporphyrins ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of exogenous carbon monoxide-releasing molecules 2 (CORM-2) on the vitality and toxicity of E. coli ATCC 25922, and to analyze the potential mechanism.

METHODS(1) In vitro experiments. Standard strains of E. coli ATCC 25922 were divided into groups A (without addition), B, C, D, and E according to the random number table, and then the latter 4 groups were respectively cultured with 1.2 mmol/L CORM-2, 1.6 mmol/L CORM-2, 1.2 mmol/L inactive CORM-2 (iCORM-2), 1.6 mmol/L iCORM-2, with six samples in each group. After being cultured for 0, 3, 5, 8, 10, 12, 16, 20, 24, 27, 30, 48 hours, proliferative vitality of E. coli was examined (denoted as absorption value under 600 nm wavelength), and bacteria number was counted. Other standard strains of E. coli ATCC 25922 were divided into groups F (without addition) and G (cultured with 0.8 mmol/L CORM-2), the expressions of genes fliA, dnaK, marA, and waaQ related to E. coli were detected by quantitative real-time (qRT)-PCR. (2) In vivo experiments. Other standard strains of E. coli ATCC 25922 were grouped as A', B', C', D', and E' and treated with the same method as that in groups A, B, C, D, and E, and 0.5 mL bacterial liquid of each group were collected when the absorption value of bacterial liquid in group A' was equal to 0.4 (under 600 nm wavelength). Seventy-two C57BL/6 mice were divided into groups, namely blank control (without treatment), H, I, J, K, and L according to the random number table, with 12 mice in each group. The mice in the latter 5 groups were intraperitoneally injected with 0.5 mL bacterial suspension of groups A', B', C', D', and E' respectively. After injection, general condition of mice in groups H, I, J, K, and L was observed. The serum levels of TNF-α and IL-6 were determined at post injection hour (PIH) 6, 12. The liver and lung samples were harvested for determination of myeloperoxidase (MPO) activity at PIH 12. The same process was carried out in blank control group. Data were processed with repeated measure analysis of variance (ANOVA), factorial design ANOVA, one-way ANOVA, and t test.

RESULTS(1) In vitro experiments. Compared with those of groups A and D, the proliferative vitality and bacteria number of E. coli in group B were all decreased (with F values respectively 1170.80, 217.52, P values all below 0.01). Compared with those of groups A and E, the proliferative vitality and bacteria number of E. coli in group C were also obviously decreased (with F values respectively 7948.34, 14 432.85, P values all below 0.01). Compared with those in group F, the expression of fliA was downregulated, while the expressions of dnaK, marA, and waaQ were upregulated in group G (with t values 30.28, -165.54, -168.88, -187.28, P values all below 0.01). (2) In vivo experiments. Symptoms including listlessness and tachypnea were observed in mice in groups H, K, and L, and they were ameliorated or not obvious in groups I and J. At PIH 6, the serum levels of TNF-α and IL-6 in groups H and K were respectively (647.3 ± 3.8) pg/mL, (3.44 ± 0.22) ng/mL and (639.3 ± 0.8) pg/mL, (2.47 ± 0.32) ng/mL, which were obviously higher than those in group I [(124.6 ± 10.7) pg/mL, (1.03 ± 0.16) ng/mL, with t values from 15.22 to 84.03, P values all below 0.01]. The serum levels of TNF-α and IL-6 in group J at PIH 6, 12 were also obviously decreased as compared with those in groups H and L (with t values from 19.27 to 245.34, P values all below 0.01). MPO activity of liver and lung tissues were significantly attenuated in group I at PIH 12 as compared with those in groups H and K, and it was also attenuated in group J when compared with those in groups H and L (with t values respectively from 17.36 to 18.92 and 2.35 to 3.61, P values all below 0.01).

CONCLUSIONSCORM-2 can obviously inhibit the vitality and toxicity of E. coli, which might be attributable to regulation of expressions of genes fliA, dnaK, marA, and waaQ of E. coli.

Animals ; Carbon Monoxide ; metabolism ; DNA-Binding Proteins ; metabolism ; Escherichia coli ; drug effects ; metabolism ; physiology ; Escherichia coli Proteins ; metabolism ; Glycosyltransferases ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; Interleukin-6 ; blood ; Liver ; enzymology ; Lung ; enzymology ; Mice ; Mice, Inbred C57BL ; Organometallic Compounds ; pharmacology ; Peroxidase ; metabolism ; Sigma Factor ; metabolism ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEIn order to get the method to improve the salt resistance of seeds and seedlings for Cassia obtusbifolia under NaCl stress, seed germination and physiological characteristics of C. obtusifolia seedlings were studied.

METHODSeveral physiological indexes of C. obtusifolia seeds treated with exogenous carbon monoxide donor hematin under NaCl stress like the germination vigor, germination rate, germination index and vigor index were measured. And other indexes like the relative water content, the contents of photosynthetic pigment, chlorophyll fluorescence parameters, the contents of soluble sugar, protein and proline, malondialdehyde (MDA), the activities of superoxide (SOD), peroxidase (POD) and catalase (CAT) were also measured.

RESULTThe germination indexes of C. obtusifolia seeds under NaCl stress had been inhibited obviously. But after the treatment of hematin, every germination indexes were all increased. The result showed that the treatment of exogenous CO donor hematin obviously improved the germination vigor, germination rate, germination index and vigor index, increased the content of chlorophyll a, chlorophyll b, total chlorophyll, improved the photochemical efficiency of photosystem II (Fv/Fm), photochemical efficiency (Fv'/Fm'), PS II actual photochemical efficiency (phiPS II), photochemical quench coefficient (qP), decreased non-photochemical quenching coefficient (NPQ) and the content of malondialdehyde (MDA) , increased the relative water content of leaves and the content of soluble surge, protein and proline. Meanwhile, the results also indicated that CO improved the activities of superoxide (SOD), peroxidase (POD) and catalase (CAT). The effects of CO could be reversed when CO scavenger Hb is added.

CONCLUSIONExogenous CO donor hematin with appropriate concentration could significantly alleviate the damages to the seeds and seedlings of C. obtusifolia under NaCl stress and promote the salt resistance of the seeds and seedlings through improving the germination indexes, the photochemical efficiency and the antioxidase activities of the seedlings.

Carbohydrates ; analysis ; Carbon Monoxide ; metabolism ; Cassia ; drug effects ; growth & development ; metabolism ; Catalase ; metabolism ; Chlorophyll ; metabolism ; Germination ; drug effects ; physiology ; Hemin ; metabolism ; pharmacology ; Malondialdehyde ; metabolism ; Peroxidase ; metabolism ; Photosystem II Protein Complex ; metabolism ; Plant Proteins ; metabolism ; Proline ; metabolism ; Seedlings ; drug effects ; growth & development ; metabolism ; Seeds ; growth & development ; Sodium Chloride ; pharmacology ; Superoxide Dismutase ; metabolism ; Time Factors ; Water ; metabolism

OBJECTIVETo identify the gene expression profiles associated with the apoptosis of pulmonary arterial smooth muscle cells stimulated by carbon monoxide (CO).

METHODSPrimary cultured Sprague-Dawley rat pulmonary arterial smooth muscle cells (PASMC) were stimulated by platelet-derived growth factor (PDGF, 20 ng/mL) and hemin (20 μmol/L). Cells were harvested after 2 hrs and Affymetrix microarrays were used to detect the gene expression profile.

RESULTSSome genes associated with Map2k3 (P38) signal pathway, such as CyclinD1, CyclinH, CyclinL1, MAP2K3, Kras and Nras, were upregulated, but P27 expression was downregulated after PDGF treatment. After endogenous CO treatment, some genes associated with P53 pathway, such as Gadd45α, P21 and Trp53inp1, were upregulated.

CONCLUSIONSP53 pathway probably plays an important role in apoptosis of pulmonary arterial smooth muscle cells treated with endogenous CO.

Animals ; Apoptosis ; Carbon Monoxide ; physiology ; Gene Expression Profiling ; Hemin ; pharmacology ; Male ; Muscle, Smooth, Vascular ; pathology ; Myocytes, Smooth Muscle ; pathology ; Pulmonary Artery ; pathology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Suppressor Protein p53 ; physiology ; p38 Mitogen-Activated Protein Kinases ; physiology

Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K+ channel is known as an important O2-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca2+-activated K+ channel (BK(Ca)), a stimulator of guanylate cyclase, and an O2-mimetic agent in heme moiety-dependent O2 sensing mechanisms. Here we compared the effects of CO on the HPV (Po2, 3%) in isolated pulmonary artery (HPV(PA)) and in blood-perfused/ventilated lungs (HPV(lung)) of rats. A pretreatment with CO (3%) abolished the HPV(PA) in a reversible manner. The inhibition of HPV(PA) was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPV(lung) was only partly decreased by CO. Moreover, the partial inhibition of HPV(lung) by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPV(PA) and HPV(lung) were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BK(Ca). As a whole, CO inhibits HPV(PA) via activating guanylate cyclase. The inconsistent effects of ODQ on HPV(PA) and HPV(lung) suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate.
Animals ; Anoxia/*physiopathology ; Carbon Monoxide/*pharmacology ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; NG-Nitroarginine Methyl Ester/chemistry/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Oxadiazoles/chemistry/pharmacology ; Pulmonary Artery/*physiopathology ; Quinoxalines/chemistry/pharmacology ; Rats ; Tetraethylammonium/chemistry/pharmacology ; Vasoconstriction/*drug effects/physiology

OBJECTIVETo explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats.

METHODSTwenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry.

RESULTSThe contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01).

CONCLUSIONAging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

Aging ; physiology ; Animals ; Carbon Monoxide ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Male ; Penis ; metabolism ; Rats ; Rats, Wistar

Animals ; Antioxidants ; metabolism ; Apoptosis ; Carbon Monoxide ; physiology ; Heme Oxygenase-1 ; physiology ; Hemoglobins ; metabolism ; Humans ; Iron ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress

AIMTo investigate the protective role of HO/CO systems in IL-1beta induced islest apoptosis and to explore the mechanisms of the protective effect of fructose-1, 6-disphosphate (FDP).

METHODSThe pancreases of the rats were removed to collect islets cells. The cells were incubated with IL-1beta with/or FDP. Cell activity, insulin secretion, HO-1 activity, CO content and apoptotic percentage were detected.

RESULTSHO-1 activity and CO content of the normal control group were low. IL-1beta induced a significant decrease of cell activity and insulin release, flow cytometry analysis showed that apoptotic percentage of islet cells remarkably increased following the addition of IL-1beta, FDP obviously improved the islets cellular activity damaged by IL-1beta, and basic amount of insulin secretion and stimulated by high glucose were improved (P < 0.01). Content of CO and activity of HO-1 were higher in the IL-1beta group than the normal control group (P < 0.05), and there were significant differences between the FDP groups and IL-1beta group. FDP decreased cell apoptotic percentage. Activities of HO-1 and content of CO were higher than that in the IL-1beta group (P < 0.01).

CONCLUSIONFDP can attenuate the IL-1beta induced apoptosis of cultured beta cells, the mechanism of which may be improved HO-1 activity and CO content.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Carbon Monoxide ; metabolism ; Cells, Cultured ; Female ; Fructosediphosphates ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; physiology ; Insulin ; secretion ; Interleukin-1beta ; antagonists & inhibitors ; pharmacology ; Islets of Langerhans ; cytology ; Male ; Rats ; Rats, Wistar