PGC-1α-Mediated Mitochondrial Biogenesis is Involved in Cannabinoid Receptor 2 Agonist AM1241-Induced Microglial Phenotype Amelioration.

Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1α is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10 ng/ml lipopolysaccharide (LPS) plus 10 U/ml interferon γ (IFNγ) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 µM AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), compared to the cells treated with LPS plus IFNγ only (P < 0.05). By using PGC-1α-siRNA, however, we found that down-regulation of PGC-1α significantly reversed the AM1241-induced effects above (P < 0.05). According to the results in this study, we found that PGC-1α may mediate CB2R agonist AM1241-induced anti-inflammation in N9 microglial cells, and the mechanism might be associated with the enhancement of mitochondria biogenesis.

Vasonatrin peptide attenuates myocardial ischemia-reperfusion injury in diabetic rats and underlying mechanisms.

Diabetes mellitus increases morbidity/mortality of ischemic heart disease. Although atrial natriuretic peptide and C-type natriuretic peptide reduce the myocardial ischemia-reperfusion damage in nondiabetic rats, whether vasonatrin peptide (VNP), the artificial synthetic chimera of atrial natriuretic peptide and C-type natriuretic peptide, confers cardioprotective effects against ischemia-reperfusion injury, especially in diabetic patients, is still unclear. This study was designed to investigate the effects of VNP on ischemia-reperfusion injury in diabetic rats and to further elucidate its mechanisms. The high-fat diet-fed streptozotocin-induced diabetic Sprague-Dawley rats were subjected to ischemia-reperfusion operation. VNP treatment (100 µg/kg iv, 10 min before reperfusion) significantly improved the instantaneous first derivation of left ventricle pressure (±LV dP/dtmax) and LV systolic pressure and reduced LV end-diastolic pressure, apoptosis index, caspase-3 activity, plasma creatine kinase (CK), and lactate dehydrogenase (LDH) activities. Moreover, VNP inhibited endoplasmic reticulum (ER) stress by suppressing glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). These effects were mimicked by 8-bromine-cyclic guanosinemonophosphate (8-Br-cGMP), a cGMP analog, whereas they were inhibited by KT-5823, the selective inhibitor of PKG. In addition, pretreatment with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress, could not further promote the VNP's cardioprotective effect in diabetic rats. In vitro H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation and incubated with or without VNP (10(-8) mol/l). Gene knockdown of PKG1α with siRNA blunted VNP inhibition of ER stress and apoptosis, while overexpression of PKG1α resulted in significant decreased ER stress and apoptosis. VNP protects the diabetic heart against ischemia-reperfusion injury by inhibiting ER stress via the cGMP-PKG signaling pathway. These results suggest that VNP may have potential therapeutic value for the diabetic patients with ischemic heart disease.

Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart.

BACKGROUND/AIMS: Neuronostatin, derived from the somatostatin preprohormone, was recently identified to be produced by several tissues exerting a role in cardiovascular regulation and metabolism. Nonetheless, the precise mechanism behind neuronostatin-elicited myocardial responses remains elusive. METHODS: This study was designed to elucidate the impact of neuronostatin on cardiac contractile function and the underlying mechanism of action involved. Adult male C57 BL/6 mice were subjected to a bolus injection of neuronostatin (50 µg/kg, i.p.). Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ handling properties were monitored to evaluate the effect of neuronostatin on cardiac function. Western blot analysis was used to examine potential signaling mechanisms involved. RESULTS: Neuronostatin administration suppressed myocardial and cardiomyocyte contractile function and disturbed intracellular Ca2+ homeostasis. We observed enlarged LVESD (with unchanged LVEDD), reduced fractional shortening, depressed peak shortening, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca2+, and prolonged relengthening duration in hearts from neuronostatin-treated mice. These effects were accompanied by downregulation of phosphorylation of sarcoplasmic reticulum Ca2+- ATPase (SERCA) and phospholamban (PLB) and activation of AMPK. CONCLUSION: Our data suggest that the cardiac depressant properties of neuronostatin possibly associated with loss of SERCA phosphorylation and AMPK activation. These findings revealed a potent inhibitory capacity for neuronostatin on cardiac function, the physiological relevance of which deserves further study.

Assessment of left ventricular myocardial systolic acceleration in diabetic rats using velocity vector imaging.

OBJECTIVES: The purpose of this study was to investigate how the myocardial acceleration during isovolumic contraction changed in rats with diabetic cardiomyopathy and a normal left ventricular ejection fraction (LVEF) by using velocity vector imaging. METHODS: Velocity vector imaging was performed in 12 control rats and 15 rats with streptozotocin-induced diabetic cardiomyopathy 12 weeks after streptozotocin injection. The segmental radial displacement, velocity, acceleration, and percent wall thickening were measured at the mid-left ventricular (LV) level. RESULTS: Compared to control rats, rats with cardiomyopathy had a significant decrease in the peak radial acceleration during isovolumic contraction in most segments of the LV wall (including the anterior, anterolateral, inferolateral, and inferior segments; P < .05) but a similar LVEF, fractional shortening, and segmental displacement. Rats with cardiomyopathy also had a significant increase in LV end-diastolic and end-systolic diameters when corrected for body mass (P < .001; P = .003, respectively) and a significant decrease in the radial peak systolic velocities of the inferolateral and inferior wall segments (P < .05). In addition, rats with cardiomyopathy had a significant decrease in the peak radial diastolic acceleration in most segments of the LV wall (except for the anterolateral one; P< .05) but similar peak radial diastolic velocities in all LV wall segments compared to controls. Pathologic examination in rats with cardiomyopathy revealed ultrastructural impairment of the capillary and cardiocyte without any atherosclerotic lesion in the coronary artery compared to control rats. CONCLUSIONS: Myocardial acceleration during isovolumic contraction decreases in rats with diabetic cardiomyopathy and a preserved LVEF, suggesting the presence of regional LV systolic dysfunction.

Achyranthes bidentata polypeptides reduces oxidative stress and exerts protective effects against myocardial ischemic/reperfusion injury in rats.

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP.

The left ventricular intracavitary vortex during the isovolumic contraction period as detected by vector flow mapping.

AIMS: The purpose of this study was to characterize left ventricular (LV) intracavitary flow during the isovolumic contraction (IVC) period in humans using vector flow mapping. METHODS: Color flow Doppler imaging was performed from the apical long-axis view in 61 patients with heart failure and 58 healthy volunteers. Doppler flow data obtained during IVC were analyzed offline with vector flow mapping. RESULTS: A large vortex was formed from the LV inflow toward the outflow during IVC. In normal subjects, the area of the vortex was sustained, but the flow volume decreased significantly during IVC (P < 0.001). A significant apex-to-base flow velocity gradient was shown along the outflow axis on aortic valve opening. However, both the area and flow volume of the vortex decreased more severely during IVC in the patients (P < 0.001). The apex-to-base flow velocity gradient along the outflow axis disappeared and a reversed velocity gradient was observed at the basal-mid level on aortic valve opening. In multivariate models, a decreased LV ejection fraction was the only independent predictor of the percentage decrease in area of the vortex during the IVC (P < 0.001), and a larger QRS width (P = 0.028) and LV end-systolic long diameter (P = 0.002) were independent predictors of the percentage decrease in flow volume of the vortex. CONCLUSIONS: The vortex across the LV inflow-outflow region during IVC facilitates the ejection of blood during early systole, and an unsustained vortex may be associated with impaired cardiac function.

Protective effects of vasonatrin peptide against hypobaric hypoxia-induced pulmonary hypertension in rats.

1. The aim of the present study was to investigate the in vivo effects of vasonatrin peptide (VNP) on hypoxia-induced pulmonary hypertension (HPH). 2. The HPH model was developed by subjecting rats to hypobaric hypoxia. The HPH rats were then treated with either VNP (50 microg/kg per day, i.p.) or saline (0.5 mL, i.p.) every day for 7 days. Haemodynamic indices, right ventricular hypertrophy (RVH) and remodelling of the pulmonary arteries were evaluated. In addition, plasma levels of atrial natriuretic peptide (ANP), endothelin (ET)-1 and angiotensin II (AngII) were determined, as was natriuretic peptide receptor-C (NPR-C) mRNA expression in the right ventricle. 3. Hypobaric hypoxia induced severe HPH compared with the normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, significantly lower levels of plasma ET-1 and AngII and cardiac NPR-C mRNA expression were observed in VNP-treated compared with saline-treated HPH rats, whereas higher plasma concentrations of ANP were found in the former group. Acute intravenous administration of 50 microg/kg VNP significantly ameliorated pulmonary haemodynamics in HPH rats. 4. Taken together, the date indicate that VNP has certain preventative and therapeutic effects against HPH.

Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP­PKG signaling.

The purpose of the present study was to explore aging­associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4­month­old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress­related protein PKR­like ER kinase, glucose­regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP­specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age­induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age­induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP­protein kinase G signaling.

B-type natriuretic peptide attenuates endoplasmic reticulum stress in H9c2 cardiomyocytes underwent hypoxia/reoxygenation injury under high glucose/high fat conditions.

Exogenously administered B-type natriuretic peptide (BNP) has been shown to provide cardioprotection against various heart diseases. However, the underlying mechanisms remain elusive. This study explores whether BNP exerts its cardioprotection against hypoxia/reoxygenation (H/R) injury under high glucose/high fat (HG/HF) conditions in cardiac H9c2 cells and uncovers the underlying mechanisms. Our data revealed that BNP significantly increased the cell viability and decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK), with a maximal effect at the BNP concentration of 10-7 mol/L. In addition, by analyzing the activation of cleaved caspase-3 and by Annexin V-FITC/PI staining, we showed that BNP attenuated H/R-induced cell apoptosis in HG/HF conditions. Western blot analysis showed enhanced phosphorylation of protein kinase RNA (PKR)-like endoplastmic reticulum (ER) kinase (PERK) and eukaryotic initiation factor 2α (eIF2α)(one of the three main signaling pathways in endoplastmic reticulum (ER) stress), and increased expression of GRP78 and CHOP proteins (ER stress-related proteins) in H9c2 cells which underwent H/R in HG/HF conditions. Treatment with BNP or 8-Br-cGMP (an analog of cGMP) reversed this activation. However, this effect was significantly weakened by KT-5823, a selective cGMP-dependent protein kinase G (PKG) inhibitor. In addition, similar to BNP, treatment with a specific inhibitor of ER stress tauroursodeoxycholic acid (TUDCA) protected the cells against H/R injury exposed to HG/HF conditions. In conclusion, these findings demonstrated that BNP effectively protected cells against H/R injury under HG/HF conditions by inhibiting the ER stress via activation of the cGMP-PKG signaling pathway.

Inhibition of cardiomyocyte contractile/relaxation by MN9202 and mechanisms involved.

BACKGROUND: The cardiac contractile function of hypertensive patients is higher than non-hypertensive patients so that it is beneficial for lowering cardiac contractile function of hypertensive patients. It remains unclear if MN9202, a dihydropyridine calcium channel blocker, has effects on positive inotropic responses induced by tetraethylammonium chloride (TEA), an antagonist of calcium-activated potassium channels, forskolin (FSK), an activator of adenylyl cyclase, isoproterenol (Iso), an activator of beta-adrenergic receptors, and methylene blue (MB), an inhibitor of guanylyl cyclase, in electrically stimulated rat cardiomyocytes. Myocyte shortening and intracellular calcium transients were assessed and the underlying mechanisms were investigated. METHODS: Twitch amplitude was measured by a video edge tracker method. Cell shortening/relengthening indexes including peak height (ph), peak height/baseline percent (ph/bl%), maximal velocity of shortening (+dL/dt), and maximal velocity of relengthening (-dL/dt) were recorded and analyzed by computer. Calcium transient amplitude (DeltaFFI) indicates intracellular calcium transients. RESULTS: Iso, FSK, TEA, and MB enhanced electrical stimulation induced contraction as evidenced by increased ph, ph/bl%, +/- dL/dt, and calcium transient amplitude (DeltaFFI) compared with those in the control group. Under basal conditions, MN9202 decreased electrically induced contraction (ph, ph/bl%,+dL/dt,-dL/dt) in a concentration-dependent manner from 3 x 10(-10) to 3 x 10(-6) mol/L. MN9202 significantly decreased calcium transient amplitude. Moreover, MN9202 (3 x 10(-6) mol/L) partially but significantly blocked the positive inotropic effect induced by Iso, FSK, MB, and TEA through blocking DeltaFFI. CONCLUSIONS: Iso, FSK, TEA, and MB increased the shortening and relengthening function of cardiomyocytes, which were partially blocked by MN9202. These results suggest that MN9202 may not only block the dihydropyridine receptor but may also inhibit other calcium influx. The exact mechanism of the action of MN9202 requires further study.

Angiogenic effects of the extracts from Chinese herbs: Angelica and Chuanxiong.

Angelica and ChuanXiong are used to cure ischemic heart disease in China. Previous studies found that these two herbs could increase myocardial blood flow, oxygen-supply and keep myocardial oxygen balance, etc. However, the mechanisms of angiogenic effects of these two herbs are not well-known. The purpose of this study was to assess the effects of Angelica and ChuanXiong on vascular endothelial growth factor (VEGF) expression in rat myocardial infarction, on endothelial cell proliferation and quantity of vessels on chick embryo chorioallantoic membrane (CAM). In this study, rats were divided randomly into either pre-treatment or acute-treatment group and sacrificed at the end of the treatments. VEGF expression using Western blot analysis was significantly increased in the groups pre-treated with ChuanXiong and Angelica when compared to the control group (p < 0.05). There was significant increase in VEGF expression in the rats treated acutely with Angelica (p < 0.05). In the contrary, the rats treated with ChuanXiong showed a decrease in VEGF expression when compared to the acute-treatment control group (p < 0.05). Similar results were observed in immunohistochemistry of VEGF expression in the myocardia. Our study also demonstrated that these two herbs significantly enhanced endothelial cell proliferation (p < 0.05) and revascularity in CAM (p < 0.05). The data showed that Angelica and ChuanXiong could affect VEGF expression in rat myocardial infarction, promote endothelial cell proliferation and stimulate quantity of vessels on CAM model. The results suggest that Angelica and ChuanXiong have angiogenic effects, and may provide some mechanisms for the treatment of myocardial infarction and peripheral ischemia.

[Effect of ginkgo biloba extract and dipyridamole on transcription and translation of inducible NO synthbase in rabbits after myocardial ischemia-reperfusion injury].

OBJECTIVE: To investigate the effects of Egb761, an extract of ginkgo biloba , and dipyridamole on inducible NO synthase (iNOS) in rabbits after myocardial ischemia-reperfusion injury. METHODS: After being established into ischemia-reperfusion injury model, 35 rabbits were divided randomly into 5 groups: Group A (the sham group), Group B (the model group), Group C (treated with dipyridamole 0.8 mg/kg), Group D (treated with Egb761, 40 mg/kg), and Group E (treated with Egb761 40 mg/kg combined with dipyridamole 0.8 mg/kg), all the medications were administered by intravenous injection 30 min after reperfusion. After administration, myocardial iNOS mRNA expression was detected by RT-PCR and western blot. RESULTS: Myocardial iNOS mRNA transcriptive expression in the 5 groups were A 0, B 157.11 +/- 17.73, C 202.6 +/- 21.84, D 356.13 +/- 24.18 and E 562.34 +/- 35.19 respectively, showing significant difference between the treated groups and group B (P <0.01). The translative expression of myocardial iNOS in the 5 groups were A 34.24 +/- 15.78, B 75.70 +/- 13.71, C 116.89 +/- 22.57, D 143.75 +/- 16.05 and E 195.09 +/- 22.25 respectively, showing significant difference between the treated groups and group B as well (P < 0.05, P < 0.01). CONCLUSION: Both Egb761 and dipyridamole could increase myocardial iNOS expression in transcriptive and translative levels in rabbits after myocardial ischemia-reperfusion injury, and the combined treatment of them shows a more significant effect.

[The study on angiogenesis activity of danggui, chuanxiong and danshen].

OBJECTIVE: To observe the effect of danggui (Radix angelicae sinensis), chuanxiong (Rhizoma chuanxiong) and danshen (Radix salvae miltionrrhizae) on cardiac microvascular endothelial cells (CMECs) obtained from rat and quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model. METHODS: Normal rat cardiac microvascular endothelial cells (CMECs) were cultured by collagenase and trypsin and the influences of the herbs on the CMECs were observed by cell count and MTT colorimetry. The activity of blood vessels was determined by quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model. RESULTS: Compared with the normal group, after treatment with chuanxiong of high dosage, danggui of high and middle dosages, danshen of high and middle and low dosages, they enhanced proliferation significantly (P < 0.05). The two later could be in dependent dose. And the herbs might increase quantitation of vessels on CAM. CONCLUSION: These Chinese herbs may promote angiogenesis by stimulating proliferation of CMEC and incresasing blood vessels.

Inhibition of hypoxia-induced proliferation and collagen synthesis by vasonatrin peptide in cultured rat pulmonary artery smooth muscle cells.

The aim of the present research is to investigate the effects of vasonatrin peptide (VNP) on hypoxia-induced proliferation and collagen synthesis in pulmonary artery smooth muscle cells (PASMCs). Smooth muscle cells isolated from rat pulmonary artery were cultured and used at passages 3-5. Cell proliferation and collagen synthesis were evaluated by cell counts, [(3)H] thymidine and [(3)H] proline incorporation. The results showed that cells exposed to hypoxia for 24 h exhibited a significant increase in [(3)H] thymidine (93%) and [(3)H] proline (52%) incorporation followed by a significant increase in cell number (47%) at 48 h in comparison with the respective normoxic controls. VNP reduced hypoxia-stimulated increase in cell proliferation in a concentration-dependent manner from 10(-8) to 10(-6) mol/L and attenuated hypoxia-induced collagen synthesis ranging from 10(-6) to 10(-5) mol/L, which is similar to but more potent than both ANP and CNP. The action of VNP on PASMCs was mimicked by 8-bromo-cGMP (10(-4) mol/L, the membrane-permeable cGMP analog), and blocked by HS-142-1 (2 x 10(-5) mol/L), the particulate guanylyl cyclase-coupled natriuretic peptide receptor antagonist, or KT-5823 (10(-6) mol/L), the cGMP-dependent protein kinase (PKG) inhibitor. The results suggest that VNP inhibits hypoxia-stimulated proliferation and collagen synthesis in cultured rat PASMCs via particulate guanylyl cyclase-coupled receptors through cGMP/PKG dependent mechanisms.

[Inhibition of moderate hypoxia-induced protein synthesis by vasonatrin peptide in cultured neonatal rat cardiomyocytes].

The present work was to investigate the effects of vasonatrin peptide (VNP) on cardiomyocyte protein synthesis induced by moderate hypoxia. In cultured neonatal rat cardiomyocytes, MTT methods, total protein measurement and (3)H-leucine incorporation were used to calculate the cell number and measure the protein synthesis of cardiomyocytes. Furthermore, radioimmunoassay was undertaken to observe the effects of VNP on the intracellular levels of cAMP, cGMP and the concentration of endothelin (ET) in the culture medium. The results showed that both the cell number and protein synthesis decreased with severe hypoxia for 24 h. In contrast, under moderate hypoxia, cardiomyocyte hypertrophy developed; the protein synthesis as evidenced by total protein content and 3H-eucine incorporation increased significantly. VNP reduced cardiomyocyte protein synthesis induced by moderate hypoxia in a dose-dependent manner. Furthermore, VNP increased the intracellular level of cGMP and decreased the concentration of ET in the culture medium under moderate hypoxia, but had no effect on the level of cAMP. These results suggest that VNP inhibits moderate hypoxia-induced protein synthesis in cultured neonatal rat cardiac myocytes. This effect is mediated, at least in part, by an increase in intracellular cGMP, a reduction in synthesis, and/or a release in ET of cardiomyocytes.

[Vasonatrin peptide attenuates the enhancement of electrically-induced intracellular calcium transient by isoproterenol in rat cardiac myocytes].

The purpose of this study was to investigate the effects of vasonatrin peptide (VNP) on electrically-induced intracellular calcium ([Ca(2+)](i)) transient and mechanism of the effects in the cardiac myocytes. The [Ca(2+)](i) transient was measured with a fluoremetric method. The effects of HS-142-1, 8-Br-cGMP and methylene blue (MB) on [Ca(2+)](i) transient in cardiac myocytes were also determined. Isoproterenol (Iso) at 10(-10)~10(-6) mol/L augmented electrically-induced [Ca(2+)](i) transient dose-dependently, which was (13+/-8)% (P>0.05), (26+/-13)% (P< 0.05), (66+/-10)% (P<0.01), (150+/-10)% (P<0.01) and (300+/-25)% (P<0.01), respectively. These effects were blocked by an beta-adrenergic bloker propranolol (10(-6) mol/L). The effect of Iso (10(-8) mol/L) on [Ca(2+)](i) transient was attenuated in a dose-dependent manner by VNP at 10(-10)~10(-6) mol/L, which was (99+/-3)% (P>0.05), (96+/-2)% (P<0.05), (84+/-6)% (P<0.01), (66+/-3)% (P<0.01) and (62+/-3)% (P<0.01), respectively. 8-Br-cGMP (10(-7)~10(-3) mol/L) aslo attenuated 10(-8) mol/L Iso-induced [Ca(2+)](i) transient dose-dependent. The effect of VNP on [Ca(2+)](i) transient was almost abolished in the presence of HS-142-1 (2x10(-5) mol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptors. MB (10(-5) mol/L), an inhibitor of GC, not only blocked the effect of VNP in myocytes, but also augmented electrically-induced [Ca(2+)](i) transient. VNP and HS-142-1 themselves did not change the [Ca(2+)](i) transient in the cardiac myocytes significantly. But MB augmented the [Ca(2+)](i) transient in the cardiac myocytes significantly. These results suggest that VNP attenuates [Ca(2+)](i) transient induced by Iso. This effect is possibly achieved by binding VNP with the natriuretic peptide GC receptors in the myocytes, leading to an increase in intracellular cGMP.

[Vasorelaxing role of vasonatrin peptide in human intramammary artery in vitro].

The purpose of this study was to investigate the vasorelaxing effect of vasonatrin peptide (VNP) on human intramammary artery (HIMA).The vasorelaxing effect of VNP on HIMA was measured by means of perfusion in vitro. The effects of HS-142-1, TEA, 8-Br-cGMP and methylene blue (MB) were also observed. It was found that VNP caused a concentration-dependent relaxation in HIMA which was independent of the endothelium. 8-Br-cGMP (0.1-1000 micromol/L) also caused a concentration-dependent relaxation in HIMA. The vasorelaxing effect of VNP disappeared in the presence of HS-142-1 (20 micromol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptor. MB (10 micromol/L), an inhibitor of GC, not only blocked completely the relaxation of HIMA, but also enhanced the vascular contraction induced by norepinephrine. TEA (1 mmol/L), an antagonist of calcium activated potassium channels (K(Ca)), reduced but not completely blocked the vasorelaxing effect of VNP. These findings suggest that VNP can relax HIMA, which is independent of the endothelium. This effect is possibly achieved by the binding of VNP with the natriuretic peptide GC receptors in the smooth muscle cells (SMCs), leading to an increase in intracellular cGMP level. Moreover, the vasorelaxing effect of VNP is associated with K(Ca).

[Progress in research on heat shock proteins in cardiovascular system].

Diverse physiological stresses (e.g., heat shock, ischemia and hemodynamics) produce multiple changes in a cell that affect metabolic processes and cellular structures. In response, stress proteins are synthesized, and are thought to mediate cytoprotection through biological function as molecular chaperones. Accumulated evidence indicates that HSP70, HSP90, HSP47, HSP32 and HSP27 play an important role during cardiac ischemia, ischemia preconditioning, cardiac hypertrophy and vascular wall injury.

Expression patterns of atrial natriuretic peptide and its receptors within the cochlear spiral ganglion of the postnatal rat.

The spiral ganglion, which is primarily composed of spiral ganglion neurons and satellite glial cells, transmits auditory information from sensory hair cells to the central nervous system. Atrial natriuretic peptide (ANP), acting through specific receptors, is a regulatory peptide required for a variety of cardiac, neuronal and glial functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors (NPR-A and NPR-C) in the inner ear, their presence within the cochlear spiral ganglion and their regulatory roles during auditory neurotransmission and development is not known. Here we investigated the expression patterns and levels of ANP and its receptors within the cochlear spiral ganglion of the postnatal rat using immunofluorescence and immunoelectron microscopy techniques, reverse transcription-polymerase chain reaction and Western blot analysis. We have demonstrated that ANP and its receptors colocalize in both subtypes of spiral ganglion neurons and in perineuronal satellite glial cells. Furthermore, we have analyzed differential expression levels associated with both mRNA and protein of ANP and its receptors within the rat spiral ganglion during postnatal development. Collectively, our research provides direct evidence for the presence and synthesis of ANP and its receptors in both neuronal and non-neuronal cells within the cochlear spiral ganglion, suggesting possible roles for ANP in modulating neuronal and glial functions, as well as neuron-satellite glial cell communication, within the spiral ganglion during auditory neurotransmission and development.

Cardiac peroxisome proliferator-activated receptor-γ expression is modulated by oxidative stress in acutely infrasound-exposed cardiomyocytes.

The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ.