OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,...OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).展开更多
Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impa...Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.展开更多
Endothelial dysfunction is the postulated link between coronary artery disease (CAD) and erectile dysfunction (ED). Brachial artery flow-mediated vasodilatation (FMD) is a non-invasive surrogate marker for endot...Endothelial dysfunction is the postulated link between coronary artery disease (CAD) and erectile dysfunction (ED). Brachial artery flow-mediated vasodilatation (FMD) is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED (assessed using the International Index of Erectile Function (IIEF-5) questionnaire); ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD (6.40%±4.60% vs. 9.10%±4.87%, P〈0.001) compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD ( ≤ 5.5%) was twice as common in ED patients (52% vs. 24% without ED). Patients with impaired FMD had higher ED prevalence (85% vs. 62%) and lower mean I IEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors (odds ratio, 2.33; 95% confidence interval: 0.59-9.23; P=0.03). An inverse correlation between FMD and ED severity was observed (r=-0.22; P=0.004). ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.展开更多
Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of v...Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.展开更多
In Chile elevated percentage of population have cardiovascular diseases, 70% of this populations is a hypertensive peoples. The Ruta graveolens (Ruta) is a medicinal plant used in different parts of the world with dif...In Chile elevated percentage of population have cardiovascular diseases, 70% of this populations is a hypertensive peoples. The Ruta graveolens (Ruta) is a medicinal plant used in different parts of the world with different therapeutics properties like dermatologic as far as anti-helmintic properties. We analyzed the vascular action measuring the tension to identify vasodilator effect of Ruta extract in norm-tense rat’s aorta incubated and measured in isolated organ bath, and evaluating the toxicity effect in CRL-1730 cell line, through enzymatic assay (MTT), confocal microscopy (propidium iodide stain) and flow cytometry (TUNEL assay), including extracellular reactive oxygen species (ROS) production through luminescence assay. The results show with DE50 29 ± 0.1 μg/mL evidenced vasodilatation, partially endothelium-depend. The cytotoxicity showed with DE50 304.6 ± 2 μg/mL in enzymatic assay (MTT) while evidenced membrane permeability in high concentrations (1500 μg/mL), DNA fragmentation in absence of oxidative stress in only observed when high concentrations of Ruta are used over the cell culture. The vasodilatation activity is executed in subtoxic concentration and partially endothelium-depend without permeability effect in the membrane and deterioration of the cells viability suggesting a complex effect of Ruta preparation in the regulation of vascular tone.展开更多
Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diab...Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diabetic patients were examined by pulse and tissue Doppler echocardiography and FMD of brachial artery. The patients were divided into 2 groups according to the size of the left ventricular relaxation parameter—E’. Results: The average age of the patients was 61 ± 6 years. FMD was 5.0 ± 1.8% in 41 patients with E’ from 3 to 7.4 cm/s (mean 6 cm/s) comparing to 5.1 ± 1.9% (p = 0.96) in 41 patients with E’ from 7.5 to 10.9 cm/s (mean 8.9 cm/s). E/E’ was 11.2 ± 2.3 in the group with lower E’ and 9.1 ± 1.6 in the group with higher E’ (p 0.001). Linear negative correlation was found between E/E’ and FMD for the patients with E’ from 3 to 7.4 cm/s (R2 = 0.131;p = 0.025) but not for the group of patients with the higher E’. The significant association between FMD and E/E’ was confirmed by multivariate analysis ((Rc)2 = 0.233;p 0.05). Conclusion: FMD has no impact on the left ventricular relaxation. However FMD is negatively associated with E/E’ in Type 2 diabetic patients who have low E’ as a sign of an impaired early relaxation.展开更多
Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic ...Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)effects.The increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor),respectively,indicating an endothelium-dependent vasodilation via the PI3K/AKT-e NOS pathway(P<0.01).Conclusion:This study provides a strategy for rapidly and precisely elucidating GXⅡ's representative in/ex vivo cardioprotective absorbed bioactive compounds(ABCs)-FTA,suggesting its potential in advancing precision ethnomedicine.展开更多
基金The project supported by National Natural Science Foundation of China(81374003)National Major Scientific and Technological Specialized Project for the Significant Formulation of New Drugs,China(2011ZX09101-002-07)Zhejiang province health high-level innovative talents training project
文摘OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).
文摘Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.
文摘Endothelial dysfunction is the postulated link between coronary artery disease (CAD) and erectile dysfunction (ED). Brachial artery flow-mediated vasodilatation (FMD) is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED (assessed using the International Index of Erectile Function (IIEF-5) questionnaire); ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD (6.40%±4.60% vs. 9.10%±4.87%, P〈0.001) compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD ( ≤ 5.5%) was twice as common in ED patients (52% vs. 24% without ED). Patients with impaired FMD had higher ED prevalence (85% vs. 62%) and lower mean I IEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors (odds ratio, 2.33; 95% confidence interval: 0.59-9.23; P=0.03). An inverse correlation between FMD and ED severity was observed (r=-0.22; P=0.004). ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.
基金supported in part by the National Natural Science Foundation of China,No.81100939 and 81773713(to WH),No.81501610(to XC)the Research Project funded by Jiangsu Provincial Government of China,No.BRA2018223(to DGM)+2 种基金the Public Health Center at Jiangnan University of China,No.JUPH201808(to XSW)the Wuxi Commission of Public Health and Family Planning of China,No.MS201717(to XSW)the Project of Academic Development Program by Governments of Jiangsu Province and Nantong City of China(to DGM)
文摘Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.
文摘In Chile elevated percentage of population have cardiovascular diseases, 70% of this populations is a hypertensive peoples. The Ruta graveolens (Ruta) is a medicinal plant used in different parts of the world with different therapeutics properties like dermatologic as far as anti-helmintic properties. We analyzed the vascular action measuring the tension to identify vasodilator effect of Ruta extract in norm-tense rat’s aorta incubated and measured in isolated organ bath, and evaluating the toxicity effect in CRL-1730 cell line, through enzymatic assay (MTT), confocal microscopy (propidium iodide stain) and flow cytometry (TUNEL assay), including extracellular reactive oxygen species (ROS) production through luminescence assay. The results show with DE50 29 ± 0.1 μg/mL evidenced vasodilatation, partially endothelium-depend. The cytotoxicity showed with DE50 304.6 ± 2 μg/mL in enzymatic assay (MTT) while evidenced membrane permeability in high concentrations (1500 μg/mL), DNA fragmentation in absence of oxidative stress in only observed when high concentrations of Ruta are used over the cell culture. The vasodilatation activity is executed in subtoxic concentration and partially endothelium-depend without permeability effect in the membrane and deterioration of the cells viability suggesting a complex effect of Ruta preparation in the regulation of vascular tone.
文摘Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diabetic patients were examined by pulse and tissue Doppler echocardiography and FMD of brachial artery. The patients were divided into 2 groups according to the size of the left ventricular relaxation parameter—E’. Results: The average age of the patients was 61 ± 6 years. FMD was 5.0 ± 1.8% in 41 patients with E’ from 3 to 7.4 cm/s (mean 6 cm/s) comparing to 5.1 ± 1.9% (p = 0.96) in 41 patients with E’ from 7.5 to 10.9 cm/s (mean 8.9 cm/s). E/E’ was 11.2 ± 2.3 in the group with lower E’ and 9.1 ± 1.6 in the group with higher E’ (p 0.001). Linear negative correlation was found between E/E’ and FMD for the patients with E’ from 3 to 7.4 cm/s (R2 = 0.131;p = 0.025) but not for the group of patients with the higher E’. The significant association between FMD and E/E’ was confirmed by multivariate analysis ((Rc)2 = 0.233;p 0.05). Conclusion: FMD has no impact on the left ventricular relaxation. However FMD is negatively associated with E/E’ in Type 2 diabetic patients who have low E’ as a sign of an impaired early relaxation.
基金Supported by the National Natural Science Foundation of China (No.81973589)。
文摘Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)effects.The increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor),respectively,indicating an endothelium-dependent vasodilation via the PI3K/AKT-e NOS pathway(P<0.01).Conclusion:This study provides a strategy for rapidly and precisely elucidating GXⅡ's representative in/ex vivo cardioprotective absorbed bioactive compounds(ABCs)-FTA,suggesting its potential in advancing precision ethnomedicine.