Effect of Basicity on the Microstructure of Sinter and Its Application Based on Deep Learning.

The influence of the evolution rule of basicity (0.6∼2.4) on the mineral composition and microstructure of sinter is studied by using a polarizing microscope, and the comprehensive application analysis of the drum index, vertical sintering speed, and yield of sinter shows that, over the course of an increase in basicity (0.6∼1.0), the mineral structure changed from the original porphyritic-granular structure to a porphyritic structure. At the same time, there was no calcium ferrite phase in the bonding phase at a basicity of less than 1.0; therefore, the downward trend of the three indicators is obvious. When the basicity was further increased to approximately 1.6, the main structure of the mineral phase changed from a corrosion structure to an interweaving corrosion structure. Because of the existence of a porphyritic-granular structure, the structure of the mineral phase was extremely inhomogeneous and most complex near the basicity of 1.6; although a small amount of calcium ferrite displayed an acicular structure, the drum index appeared to show a very low value. With an increase in basicity to 2.0, the mineral phase structure was dominated by an interweaving corrosion structure with a uniform framework, and the content of calcium ferrite reached the highest value. Moreover, a clear acicular structure developed, and the drum index also increased to the highest value. At a basicity of more than 2.0, a mineral structure began to appear and the corrosion, porphyritic-granular structure, and the drum index also showed a slightly declining trend. Therefore, in the actual production process, basicity should be avoided as far as possible at around 1.0 and 1.6 and it should be controlled at around 2.0. At the same time, based on the mineral facies data set of this paper, the convolutional neural network is used to carry out a simple prediction model experiment on the basicity corresponding to the mineral facies photos, and the effect is quite good, which provides a new idea and method for the follow-up study of mineral facies.

Angiotensin II type i receptor agonistic autoantibodies induces apoptosis of cardiomyocytes by downregulating miR21 in preeclampsia: a mechanism study.

Angiotensin II type I receptor agonistic autoantibodies (AT1-AA) in the plasma of preeclampsia patients can induce apoptosis of cardiomyocytes, and microRNA-21 (miR-21) can exert a protective effect on cardiomyocytes. But whether the pro-apoptotic effect of AT1-AA is associated with miR-21 is unclear. The objective of the present study was to explore whether AT1-AA induced cardiomyocyte apoptosis was related to its inhibitory of miR-21 expression. In vivo studies, the pregnant rats were divided into two groups: Sham group, Model group. The pathology, cell apoptosis, and relative protein expressions were evaluated by hematoxylin and eosin staining, and Western blot assay. The expression of microRNA was detected by gene microarray. In the cell experiment, the neonatal rat cardiomyocytes were divided into four groups: NC group, AT1-AA group, and miR-21 group and AT1-AA+miR-21 group. The cell apoptosis and relative proteins' expressions were measured by flow cytometry and Western blot assay. Results: Compared with the Sham group, miR-21 in the cardiac tissue of the model group was downregulated significantly; the expression of p-JNK, Bax and caspases-3 was increased, the expression of Bcl-2 was decreased, and the Bcl-2/Bax ratio became smaller. The expression of miR-21 in AT1-AA treated cardiomyocytes was only 52% of the control group, with an apoptosis rate of 32.6%. In addition, the expression of pPTEN, pAKT and pFOXO3a in the model group was significantly higher than that in the NC group. The cardiomyocyte apoptosis rate in miR-21 overexpression group was only 23.7%, which was higher than that in the NC group, but significantly lower than that in AT1-AA group. PTEN, AKT and FOXO3a phosporylation in miR-21 overexpression group was also lower than that in AT1-AA group. AT1-AA induced cardiomyocyte apoptosis by downregulating miR-21, and the PTEN/AKT/FOXO3a signal transduction pathway participated in this process. The result of the present study suggests that miR-21 may prove to be a new target for the diagnosis and treatment of preeclampsia and other cardiovascular diseases.

Effects and molecular mechanisms of AT1-AA in retinopathy of preeclampsia.

Preeclampsia not only seriously endangers maternal and fetal health during pregnancy but may incur many sequelae in postpartum women such as reduced visual acuity. Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) is closely associated with preeclampsia. The aim of the present study is to determine whether AT1-AA is associated with retinal impairment during the course of preeclampsia. A preeclampsia model was established by injecting AT1-AA into pregnant rats via the tail vein. Changes in the retinal histological structure were observed. Cell apoptosis and cytokines including reactive oxygen species (ROS), as well as apoptosis-related proteins such as Bcl-2, Bax, and caspase-3 were detected. In addition, flash electroretinograms obtained at different postpartum days were analyzed. Compared with the control group, the retinal structure became edematous and the cell density was reduced significantly in preeclampsia group. The cell apoptosis rate was increased significantly. In addition, the content of ROS, the levels of Bax and caspase-3 in the retina were increased, while the content of Bcl-2 was reduced significantly. Continuous observation of the electroretinograms showed loss of retinal ganglion cells postpartum. The present study demonstrated that AT1-AA induced retinal cell apoptosis by promoting ROS release and activating caspase, suggesting that the increased postpartum susceptibility of preeclamptic women to retinopathy is related to AT1-AA-induced cell apoptosis.

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats.

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70µg/15ml or 350µg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70µg/15ml) or budesonide (250µg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

Role and mechanism of AT1-AA in the pathogenesis of HELLP syndrome.

HELLP syndrome remains a leading cause of maternal and neonatal mortality and morbidity worldwide, which symptoms include hemolysis, elevated liver enzymes and low platelet count. The objective of this study was to determine whether HELLP is associated with AT1-AA. The positive rate and titer of AT1-AA in plasma from pregnant women were determined, and the correlation of AT1-AA titer with the grade of HELLP was analyzed. A HELLP rat model established by intravenous injection of AT1-AA. Our experimental results show the AT1-AA titer and positive rate were significantly higher in HELLP group, and AT1-AA titer were positively correlated with the level of TNF-α and ET-1 in plasma and the grade of HELLP syndrome. The results of animal experiments showed that the typical features of HELLP in the pregnant rats after AT1-AA injection. The levels of TNF-α and ET-1 in plasma and liver tissue were significantly increased in AT1-AA-treated rats compared with control rats. The HELLP syndrome induced by AT1-AA was attenuated markedly after administration of losartan. These data support the hypothesis that one the potential pathway that AT1-AA induce damage to capillary endothelial cells and liver during pregnancy is through activation of TNF-α and ET-1.

Chronic fatigue syndrome in Chinese middle-school students.

The objective of the present study was to determine the prevalence of chronic fatigue syndrome (CFS) and its associated factors in middle-school students in Suzhou, China. From September 2010 to January 2011, across-sectional study was conducted in junior- and senior middle-school students aged 10 to 18 years using a battery of confidential questionnaires. Our results indicate that 18,139 completed the questionnaires effectively, of whom 163 (0.9%) met the definition of CFS, with senior high-school students and male students predominating. The prevalence of CFS in the middle-school students increased steadily with age. The main symptoms of CFS in these students included being afraid of going to school, despondency, and irritability in addition to those specified in the Centers for Disease Control and Prevention (CDC). Our study shows that CFS is prevalent among Chinese teenagers, and requiring proper intervention and treatment.

Roles and possible mechanisms of autoantibodies against the angiotensin AT1 receptor in vascular calcification of rats.

The aim of this study was to investigate the effect of AT1-AAs on vascular calcification. Wistar rats were immunized with synthetic peptides corresponding to the second extracellular loop of AT1 receptor. The titer of AT1-AAs in rat serum, SBP, and HR were detected weekly. Histological analysis and biochemical parameters were measured 4 months after initial immunization. The level of osteopontin and osteocalcin was measured by Western blot analysis. The results showed that the titer of AT1-AAs, SBP, and HR were all increased significant 4 weeks after initial immunization. Compared with the control group, the contractile force of the aortic ring of the immunized group to phenylephrine was significantly higher, and relaxation function was significantly reduced. The ALP activity and protein levels of osteoporotin and osteocalcin were increased in the aortic tissue of the immunized group. Histological examination showed varying degrees of calcification within each cell layer with von Kossa staining in the immunized group. Losartan treatment not only significantly lowered SBP and HR to the similar level of the control group but inhibited the ALP activity and protein levels of osteoporotin and osteocalcin. Our study demonstrated that AT1-AAs contributed to the progression of vascular calcification, suggesting that AT1-AAs may play a vital role in the occurrence of cardiovascular disease in patients with severe hypertension.

Multiple cardiac arrests induced by pulmonary embolism in a traumatically injured patient: A case report and review of the literature.

RATIONALE: Pulmonary embolism-induced cardiac arrest should not be given up arbitrarily, knowing that the etiology of pulmonary embolism is reversible in most cases. PATIENT CONCERNS: We present a case of continuous resuscitation lasting approximately 4 hours, during which 21 episodes of cardiac arrest occurred in a 46-year-old man who sustained high-level paraplegia after a road traffic accident. DIAGNOSES: Multiple cardiac arrests induced by pulmonary embolism. INTERVENTIONS: The patient received cardiopulmonary resuscitation and thrombolytic therapy. OUTCOMES: The patient was discharged in 2 weeks when his condition turned for the better. LESSONS: Cardiopulmonary resuscitation of patients with pulmonary embolism-induced cardiac arrest should not be given up arbitrarily, knowing that the etiology of pulmonary embolism is reversible in most cases. Effective external cardiac compression can not only save the patient's life but also attenuate neurological sequelae. Thrombolytic therapy is the key to the final success of resuscitation.

Role of agonistic autoantibodies against type-1 angiotensin II receptor in the pathogenesis of retinopathy in preeclampsia.

To investigate the mechanism underlying AT1-AA-induced retinopathy in severe preeclampsia by measuring the positive rate and titer of AT1-AA in plasma from women with severe preeclampsia and normal pregnant women to see whether AT1-AA titer was correlated with the grade of retinopathy. A preeclampsia rat model was also established by intravenous injection of AT1-AA extracted from the plasma of patient suffering from severe preeclampsia. The results showed that the plasma titer and positive rate of AT1-AA were significantly higher in women with severe preeclampsia than normal pregnant women. The antibody titer in cases of severe preeclampsia was associated with the grade of retinopathy, and positively correlated with the level of TNF-α and VEGF. The animal experiment results showed that the modeled rats presented symptoms very similar to symptoms of human preeclampsia, including retinopathy. Ocular fundus examination showed retinal microvascular abnormalities, hemorrhaging and leakage in the severe preeclampsia. Morphological changes included edema, thickening of the INL and ONL, and pigment atrophy. TNF-α and VEGF levels were increased in the vitreous humor and retina of the model rats. Our studies results suggest that abnormal expression of AT1-AA could induce damage to retinal capillary endothelial cells and increase vascular permeability, resulting in retinopathy.

Mechanism of agonistic angiotensin II type I receptor autoantibody-amplified contractile response to Ang II in the isolated rat thoracic aorta.

Agonistic autoantibody to the angiotensin II type I receptor (AT1-AA) is highly associated with preeclampsia by increasing the sensitivity of Ang II during pregnancy in rats, thus leading to a preeclampsia-like syndrome. However, the mechanism underlying this phenomenon remains unclear. The purpose of this study was to observe AT1-AA amplification of Ang II-induced vasoconstriction in rat thoracic aortic rings. It was found that exposure to low concentrations of AT1-AA (0.4 nM) caused a contraction of <5% of the maximal response to 60 mM KCl. In addition, the Ang II-induced contractile response was amplified in the presence of a threshold contraction to AT1-AA, as manifested by a leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. These results showed that preincubation with low AT1-AA could amplify the Ang II dose-response curve, and this amplification could be attenuated markedly by 0.1 µM heptapeptide AFHYESQ. In calcium-free Krebs solution, 10 µM of 2-aminoethoxydiphenyl borate (an IP3 receptor inhibitor) both blocked the AT1-AA base contraction and completely abolished the amplification. Both 5 µM of U-73122 (a phospholipase C inhibitor) and 10 µM of εV1-2 (an εPKC inhibitor) could partially inhibit the Ang II-induced contractile response. εV1-2, but not U-73122, could completely inhibit the amplification response of AT1-AA to Ang II. These results suggest that AT1-AA is able to cause amplification response to Ang II probably via the calcium-independent protein kinase C pathway, which may provide a new therapy strategy for preeclampsia.

Changes in focal adhesion kinase expression in rats with collagen-induced arthritis and efficacy of intervention with disease modifying anti-rheumatic drugs alone or in combination.

Focal adhesion kinase (FAK) is known to promote the proliferation, migration and survival of synovial cells and plays an important role in the occurrence, development and pathological process of rheumatoid arthritis (RA). The aim of the present study was to observe FAK changes in synovial cells of rats with collagen-induced arthritis (CIA) and after intervention with disease modifying anti-rheumatic drugs (DMARDs) alone or in combination in a CIA female SD rat model induced by collagen type II. The rats were randomized to 8 groups: normal control group, CIA model control group, methotrexate (MTX, 0.9 mg/kg/w) group, cyclophosphamide (CTX, 24 mg/kg/3 w) group, leflunomide (LEF, 1.2 mg/kg/d) group, MTX + CTX group, LEF + CTX group, and MTX + LEF group. They were intervened with DMARDs alone or in combination for six weeks. The experiment lasted a total of 9 weeks in vivo. Articular inflammation was measured during the process of drug intervention in terms of the degree of swelling degree in the right hind foot using a venire caliper. All animals were sacrificed by breaking the neck after 9 weeks. Then, the ankle was fixed, decalcified, embedded, and HE stained, and prepared into slices to observe pathological changes in the synovial tissue. FAK expression in synovial cells was assayed by immunohistochemistry and the mean optical density (OD) value was measured using the HPIAS-2000 image analysis system. It was found that FAK expression was negative in normal control group, positive in CIA model control group, and decreased in the three DMARD combination treatment groups significantly as compared with that in the three single-drug groups (P < 0.05). FAK expression in LEF + CTX group or MTX + CTX group decreased more significantly than that in MTX + LEF group (P < 0.05), and there was no statistically significant difference between LEF + CTX and MTX + CTX groups. The arthritis index and pathological change in the synovial tissue in LEF + CTX group or MTX + CTX group were improved more significantly than those in MTX + LEF group or single-drug groups. Our results showed that FAK expression was positive in CIA rats, indicating that it played an important role in the pathogenesis of RA, and that intervention with DMARDs could reduce the FAK expression in synovial cells of CIA rats. We hope these findings would contribute to the treatment of RA and other rheumatic diseases by reducing adhesion, proliferation and migration of synovial cells and inhibiting the over-expression of FAK.

Potentiated interaction between ineffective doses of budesonide and formoterol to control the inhaled cadmium-induced up-regulation of metalloproteinases and acute pulmonary inflammation in rats.

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases.

Exposure to AT1 receptor autoantibodies during pregnancy increases susceptibility of the maternal heart to postpartum ischemia-reperfusion injury in rats.

Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats.

Maternal treatment with agonistic autoantibodies against type-1 angiotensin II receptor in late pregnancy increases apoptosis of myocardial cells and myocardial susceptibility to ischemia-reperfusion injury in offspring rats.

Epidemiological studies have demonstrated that offspring born to mothers preeclampsia (PE) are at increased risk for developing cardiovascular diseases after birth, but the underlying mechanism is unknown. Angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of the AT1 receptor, is believed to be involved in the pathogenesis of both PE and fetal growth restriction. The aim of the present study was to confirm the hypothesis that prenatal AT1-AA exposure increases the heart susceptibility to ischemia/reperfusion injury (IRI) in the offspring in an AT1-AA-induced animal model of PE, and determine whether or not the increase of maternal AT1-AA level is a factor contributing to sustained abnormalities of the heart structure during infancy. The hearts of 45-day-old offspring rats were studied using Langendorff preparation to determine the susceptibility of the heart to IRI. The results showed that the body weight of the maternal rats was not significantly different between the study and control groups, but the body weight of their offspring in AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3 after birth. Although the heart weight index was not significantly affected at all ages examined, AT1-AA significantly increased the size of myocardial cells of the left ventricle (LV) at the age of 45 days. AT1-AA gained access to fetal circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1-AA also significantly delayed recovery from IRI and affected the LV function of 45-day-old offspring. This was associated with a significant increase in IRI-induced LV myocardial infarct size. These results suggest that AT1-AA induced abnormal apoptosis of fetal myocardial cells during the fetal period and increased the cardiac susceptibility to IRI in adult offspring.

Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA) are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191) to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day) and hyroxysafflor yellow A (HSYA) (10 mg/kg/day). The result show that systolic blood pressure (SBP) and heart rate (HR) of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.

Angiotensin II type I receptor agonistic autoantibody-induced apoptosis in neonatal rat cardiomyocytes is dependent on the generation of tumor necrosis factor-α.

Angiotensin II type I receptor agonistic autoantibodies (AT1-AA) are related to pre-eclampsia and hypertension and have a direct effect of stimulating the production of tumor necrosis factor-alpha (TNF-α) in the placenta. TNF-α is a known mediator of apoptosis. However, few studies have reported the role of TNF-α and its relationship within AT1-AA-induced apoptosis of cardiomyocytes. In this study, neonatal rat cardiomyocytes were treated with various concentrations of AT1-AA. The apoptosis of neonatal rat cardiomyocytes was determined using TUNEL assay and flow cytometry. The level of secreted TNF-α was measured by enzyme-linked immunosorbent assay, and caspase-3 activity was measured by a fluorogenic protease assay kit. AT1 receptor blockade and TNF inhibitor were added to determine whether they could inhibit the apoptotic effect of AT1-AA. Results showed that AT1-AA induced the apoptosis of neonatal rat cardiomyocytes in a dose-dependent and time-dependent manner. AT1-AA increased TNF secretion and caspase-3 activities. AT1 receptor blockade completely abrogated AT1-AA-induced TNF-α secretion, caspase-3 activation, and cardiomyocyte apoptosis. TNF-α receptor inhibitor significantly attenuated AT1-AA-induced neonatal rat cardiomyocyte apoptosis. AT1-AA in the plasma of pre-eclamptic patients promoted neonatal rat cardiomyocyte apoptosis through a TNF-caspase signaling pathway.

The effects of hydroxysafflor yellow A on blood pressure and cardiac function.

AIM OF THE STUDY: This work aims to investigate the effects of HSYA on cardiac function and blood pressure. MATERIALS AND METHODS: To evaluate changes in mean arterial pressure (MAP) and heart rate (HR), different groups of pentobarbitone-anesthetized normotensive and spontaneously hypertensive rats (SHR) were treated with intravenous HSYA (0.1-3 mg/kg). Isolated WKY rat hearts in Langendorff system were employed for examining the effect of HSYA on hemodynamic. After 30 min equilibration time the isolated hearts were perfused with HSYA (30 µmol/L) in a stepwise fashion. Potassium channel inhibitors were used to determine the role of potassium channel activation in HSYA effect. RESULTS: Intravenous injection of the HSYA significantly reduced MAP and HR in both normotensive rats and SHR in a dose-dependent manner. HSYA reduced left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase of left ventricular pressure (+dp/dt(max)) and heart rate (HR) in a dose-dependent manner. HSYA had no remarkable effect on the maximum rate of decrease of left ventricular pressure (-dp/dt(max)); BK(Ca) and K(ATP) blocker can weakened the inhibitory effect of HSYA on heart function and HR, but K(V) and K(ACh) blocker did not significantly weaken the HSYA effects. CONCLUSION: Our results show that HSYA could significantly reduce blood pressure and heart rate, which may be related to activation of BK(Ca) and K(ATP) channels.

Changes in cardiac structure and function in rats immunized by angiotensin type 1 receptor peptides.

Angiotensin II (Ang II) is known to induce cardiomyocyte hypertrophy by activating the Ang II type 1 (AT1) receptor. Some studies have demonstrated that the autoantibodies against angiotensin AT1 receptor (AT1-AAs) cause functional effects, which is similar to those observed for the natural agonist Ang II. In this study, we investigated the effects of AT1-AAs on cardiomyocytes' structure and function. Male Wistar rats were immunized with synthetic peptides corresponding to the second extracellular loop of AT1 receptor and Freund's adjuvant. The titers of AT1-AAs in rat serum were detected by enzyme-linked immunosorbent assay every week. Hemodynamic analysis and heart weight (HW) indices were measured on the 4th and 8th months after initial immunization, respectively. Cultured neonatal rat cardiomyocytes were used to observe the hypertrophic effects of AT1-AAs. Results showed that systolic blood pressure and heart rate were significantly increased, the titers of AT1-AAs were also increased after 4 weeks of initial immunization. Compared with control group, the HW/body weight (BW) and left ventricular weight/BW of immunized rats were increased significantly and cardiac function was enhanced compensatively. The cultured neonatal rat cardiomyocytes respond to AT1-AAs stimulation with increased (3)H-leucine incorporation and cell surface area in a dose-dependent manner. These results suggest that the AT1-AAs have an agonist effect similar to Ang II in hypertrophy of cardiomyocytes in vivo and in vitro. AT1-AAs are involved in the pathogenesis of cardiovascular diseases and hypertension.

Autoantibody against cardiac beta1-adrenoceptor induces apoptosis in cultured neonatal rat cardiomyocytes.

To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac beta1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the beta1-adrenoceptor to induce the production of anti-beta1-adrenoceptor antibodies in the sera. Immunoglobulin (Ig) G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an agonist-like activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with beta1-adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against beta1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of beta1-adrenoceptor.

Detection of serum autoantibodies against AT1A-receptor during the development of the four types of hypertensive rat models.

Using two-kidney one-clip renal hypertensive (2K1C group), stress-induced hypertensive (neural group), DOCA-salt treated hypertensive (DOCA group) and spontaneously hypertensive rats (SHR group), to investigate the change in AT(1A)-receptor autoantibodies (AT(1A)-AAs) during the development of the four types of hypertension. The biological activities of AT(1A)-AAs were examined. It was shown that the frequency of occurrence and titres of AT(1A)-AAs increased significantly during the development of hypertension. In the four hypertensive groups studied, the occurrence of AT(1A)-AAs was most prominent in SHR, 2K1C and neural groups. The biological effects of AT(1A)-AAs were shown to increase the beating frequency of cultured neonatal myocardial and vascular contractile tension. It is suggested that autoimmune mechanisms are involved the pathogenesis of different types of hypertension and the AT(1A)-AAs may be one of the mechanisms leading to cardiac hypertrophy.