Abstract 174: Remote Ischemic Preconditioning Improves Digital Vascular Endothelial Function and Enhances Circulating Nitric Oxide Formation in Healthy Volunteers

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jun Tao ◽  
Xinzhu Tong

Background: Remote ischemic preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against organ damage by ischemia-reperfusion. It has been reported that RIPC improves endothelial function of the forearm in normal subjects and patients with coronary artery disease. However, the digital vascular endothelial response to RIPC has not been determined in healthy volunteers. Methods: This study was performed to examine effect of RIPC on fingertip digital vascular endothelial function by using endothelial pulse amplitude tonometry (EndoPAT) device and alteration in circulating nitric oxide(NO) level in peripheral blood. Ten healthy adult subjects (5 men, 5 women, mean age 25.2 years) had 3 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Another 10 healthy volunteers (6 men, 4 women, mean age 26.2 years) were used as the control group of sham and the cuff was inflated for 3 times at 10 mmHg for 5 minutes with 5-minute intervals. Fingertip digital vascular endothelial function of the ipsilateral arm was measured prior to first ischemia, 3h and 6h after the last episode of ischemia. Blood samples were taken from the contralateral arm prior to first ischemia, 3h and 6h after the last episode of ischemia. Results: Fingertip digital vascular endothelial function was significantly increase in 3h and 6h after the last RIPC intervention compared with the baseline condition(p<0.05). In parallel the RIPC stimulus increased circulating NO formation(p<0.05). There is a close association between finger vascular endothelial function and NO formation(p<0.05). Conclusion: The present findings demonstrate for the first time that transient RIPC contributes to improvement of digital vascular endothelial function and increase in circulating NO production in healthy volunteers. Our data provide a novel evidence to support that RIPC might gain even wider application not only in disease but also in health.

2019 ◽  
Vol 126 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Jin Hee Jeong ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  

Cystic fibrosis (CF) is a genetic disorder associated with vascular endothelial dysfunction. Nitric oxide (NO) plays a major role in maintaining vascular function, and tetrahydrobiopterin (BH4) is a critical determinant of NO bioavailability. Thus the purpose of this study was to investigate the effects of oral administration of BH4 on endothelial function in patients with CF. Twenty-nine patients with CF (18 ± 8 yr old) and 29 healthy matched controls were recruited. Patients with CF participated in a randomized trial where they received a 5 mg/kg dose of oral BH4 (BH4-5; n = 17) or a 20 mg/kg dose of oral BH4 (BH4-20; n = 12). On a separate visit, a subset of patients from each group was retested following a placebo (PLC; n = 9). Brachial artery flow-mediated dilation (FMD) was used to evaluate vascular endothelial function, and a plasma sample was obtained before and 3 h after treatment. Cultured endothelial cells were treated with plasma to assess NO bioavailability. Baseline FMD was lower in patients compared with controls (5.7 ± 3.4 vs. 8.4 ± 3.5%, respectively, P = 0.005). No change in FMD was observed following PLC or BH4-5 (∆FMD: −0.8 ± 1.9% and −0.5 ± 2.5%; P = 0.273 and 0.132, respectively). Treatment with BH4-20, however, resulted in significant improvements in FMD (∆FMD: 1.1 ± 1.4%) compared with BH4-5 ( P = 0.023) and PLC ( P = 0.017). Moreover, BH4-20 significantly decreased endothelial cell superoxide production and increased NO production. These data suggest that a single oral dose of BH4 at 20 mg/kg improves vascular endothelial function in patients with CF, likely via increased endothelial NO synthase coupling. These findings support the hypothesis that loss of BH4 bioactivity contributes, in part, to endothelial dysfunction in patients with CF. NEW & NOTEWORTHY For the first time, the present study documents that a single dose of oral BH4 can improve vascular endothelial function in patients with cystic fibrosis (CF), and our in vitro data suggest this is via decreasing uncoupled nitric oxide. These data provide insight into the important role of BH4 bioactivity in vascular dysfunction and provide the foundation for further investigation into the chronic effects of BH4 treatment in patients with CF.


2021 ◽  
pp. 153537022110638
Author(s):  
Weiling Li ◽  
Shasha Liu ◽  
Yuan Li ◽  
Weijing Wang ◽  
Yiming Dong ◽  
...  

Hypertensive disorders complicating pregnancy (HDCP) is a systemic disease among pregnant women. Therefore, the prevention and prediction of hypertension during pregnancy are critical. This study aimed to clarify whether the vascular endothelial function of women with gestational hypertension was linked to placental growth factor. A total of 200 pregnant women were enrolled in our study and subsequently divided into two groups: the HDCP group and the normal pregnancy controls. The levels of serum placental growth factor, as well as plasma endothelin-1 and nitric oxide, between the two groups were measured. In addition, the endothelial function indexes, including pressure-strain elasticity coefficient (EP), the common carotid stiffness index (β), arterial compliance, single-point pulsed-wave velocity, and augment index (AI) of bilateral common carotid arteries, were compared between the HDCP and control groups using the echo tracking technique. In our study, the level of placental growth factor in the HDCP group was significantly lower than the control group. Furthermore, our results clarified that endothelin-1 increased while nitric oxide decreased in the HDCP group compared with the control group. On the other hand, we found that EP, β, pulsed-wave velocity and augment index values were significantly higher in the HDCP group than in the control group (P < 0.001). However, the value of arterial compliance was significantly decreased in patients of the HDCP group compared with the control group (P < 0.001). In conclusion, the association between serum placental growth factor and vascular endothelial function in HDCP could serve as a more accurate predictive factor of pregnant hypertension.


2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Chao Ding ◽  
Xiaohua Hu

This study is to investigate the effect of atorvastatin combined with losartan on inflammatory factors, vascular endothelial function, and cardiovascular events in patients with diabetic nephropathy. A total of 128 patients with diabetic nephropathy treated in our hospital from January 2014 to December 2015 were selected as the study subjects, and 64 cases were randomly divided into observation group and 64 cases in the control group. The control group was treated with losartan on the basis of routine treatment, and the observation group was treated with atorvastatin on the basis of the control group. The blood lipid, inflammatory factors, changes in vascular endothelial function and cardiovascular events were compared between the two groups. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the two groups before treatment ( P > 0.05); after treatment, the levels of TC, TG, and LDL-C in the observation group were significantly lower than those of the control group, and the level of HDL-C was significantly higher than that of the control group ( P < 0.05). The levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) were not statistically different between the two groups before treatment ( P > 0.05); after treatment, the levels of hs-CRP, TNF-α, and IL-6 in the observation group were significantly lower than those of the control group ( P < 0.05), the level of HDL-C was significantly higher than that of the control group ( P < 0.05). There were no significant differences in the levels of endothelin-1 (ET-1) and nitric oxide (NO) between the two groups before treatment ( P > 0.05). After treatment, the level of ET-1 in the observation group was significantly lower than that of the control group ( P < 0.05), and the level of NO was significantly higher than that of the control group ( P < 0.05). After treatment, all patients were followed up for 2 years, and the incidence of secondary cardiovascular events in the observation group was 12.50% (8/64), which was significantly lower than 29.69% (19/64) of the control group ( P < 0.05). Combination of atorvastatin and losartan can significantly improve the levels of blood lipid, inflammatory factors, and vascular endothelial function in patients with diabetic nephropathy and can effectively reduce the incidence of cardiovascular events.


Author(s):  
Meihong ZHOU ◽  
Zhaojun HUANG

Background: We aimed to explore the effect of comprehensive cerebral protection on cerebral oxygen metabolism and vascular endothelial function in elderly patients with acute cerebral infarction. Methods: A total of 168 elderly patients with acute cerebral infarction treated in The First Affiliated Hospital of Nanchang University, China from January 2016 to January 2018 were selected. The patients were divided into a control group and an observation group using random number method, n=84. Patients in the observation group were given comprehensive cerebral protection treatment, and patients in the control group were treated with conventional standardized treatments. The changes of cerebral oxygen metabolism, hemorheology and vascular endothelial function before and after treatment were compared between the two groups. Results: After treatment, oxygen content in arteries and internal jugular veins (Da-vO2), ofoxygen uptake fraction (OEF), Oxygen saturation (SpO2), nitric oxide (NO) were increased in both groups in comparison to before treatment, jugular venous oxygen saturation (SjvO2), brain oxygen uptake rate (ERO2), endothelin (ET), intracranial pressure (ICP), whole blood viscosity, plasma viscosity, reduced viscosity of whole blood, and hematocrit were decreased. However, the changes in the observation group were larger than those in the control group, the difference was statistically significant (P<0.05). Conclusion: The treatment of cerebral infarction in elderly patients with acute cerebral infarction can effectively improve the cerebral oxygen metabolism and vascular endothelial function and improve the blood rheology, which has important clinical value.


2003 ◽  
Vol 12 (2) ◽  
pp. A55
Author(s):  
Bill Bilsborough ◽  
Daniel J. Green ◽  
Cyril D.S. Mamotte ◽  
Frank M. van Bockxmeer ◽  
Gerry O'Driscoll ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
He Tai ◽  
Xiao-lin Jiang ◽  
Si-cheng Yao ◽  
Ye Liu ◽  
Hong Wei ◽  
...  

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P &lt; 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P &lt; 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P &lt; 0.05) and correlated negatively with endothelin-1 (ET-1) (P &lt; 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P &lt; 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P &lt; 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P &lt; 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P &lt; 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03575988.


Author(s):  
Peter H Lin ◽  
Debra Leslie ◽  
Mary Levine ◽  
Garth Davis ◽  
Caldwell Esselstyn

OBJECtIVE: Peripheral arterial disease (PAD) is characterized by impaired arterial circulation to the extremities caused in part by atherosclerosis. This study examined the effect of a plant-based diet (PBD) on vascular function in PAD patients.METHODs: Patients with PaD were randomized to plant-based dietary intervention (PBD group, n = 24) or no specific dietary advice (control group, n = 28). Biochemical parameters, including lipid profile and inflammatory biomarkers, and nitric oxide were measured at baseline and 4 months after dietary intervention. Vascular function including brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness(IMT), carotid-femoral pulse wave velocity (PWV), and brachial-ankle PWV were measured at baseline and 4 months after dietary intervention.RESULTS: Biochemical parameters were similar at baseline between the 2 groups. There was no change in any of the biochemical parameters in the control group at 4 months. However, patients in the PBD group had a significant improvement in lipid profile, including total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein a1 (APO-A1) levels. Greater nitric oxide and reduced high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were found in the PBD group at 4 months, whereas there were no changes in the control group. at baseline, FMD was similar between the 2 groups. after 4 months, PBD participants showed significant endothelial function improvement in FMD response and arterial stiffness response, with increased carotid-femoral and brachial-ankle PWV compared to the control group. CONCLUSIONS: A plant-based diet improves vascular endothelial function in PaD patients following 4 months of dietary intervention. This dietary intervention can result in decreased serum cholesterol and inflammatory biomarkers, which may further enhance vascular endothelial function. KEYWORDS: Plant-based diet; Vascular endothelial function; Flow-mediated dilation; Brachial artery reactivity test


2018 ◽  
Vol 315 (5) ◽  
pp. H1486-H1494 ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Gábor Csányi ◽  
Kathleen T. McKie ◽  
...  

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.


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