scholarly journals Effect of an inhaled glucocorticoid on endothelial function in healthy smokers

2008 ◽  
Vol 105 (1) ◽  
pp. 54-57 ◽  
Author(s):  
Eliana S. Mendes ◽  
Gabor Horvath ◽  
Patricia Rebolledo ◽  
Maria Elena Monzon ◽  
S. Marina Casalino-Matsuda ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Cigarette Smoking ◽  
Endothelial Function ◽  
Vascular Reactivity ◽  
Systemic Circulation ◽  
Sublingual Nitroglycerin ◽  
Proof Of Concept ◽  
Inhaled Corticosteroid ◽  
Clinical Investigations

Cigarette smoking is associated with attenuated endothelium-dependent vasodilation (endothelial dysfunction) in the systemic circulation, including the airway circulation. We wished to determine whether an inhaled corticosteroid could restore endothelial function in the airway of lung-healthy current smokers, ex-smokers, and nonsmokers. We measured baseline airway blood flow (Q̇aw) and Q̇aw reactivity to inhaled albuterol as an index of endothelium-dependent vasodilation and to sublingual nitroglycerin as an index of endothelium-independent vasodilation in lung-healthy current smokers, ex-smokers, and nonsmokers. Current smokers were then treated with inhaled fluticasone for 3 wk, and all measurements were repeated after fluticasone treatment and after a subsequent 3-wk fluticasone washout period. Baseline mean Q̇aw and endothelium-independent Q̇aw reactivity were similar in the three groups. Mean endothelium-dependent Q̇aw reactivity was 49.5% in nonsmokers, 42.7% in ex-smokers, and 10.8% in current smokers ( P < 0.05 vs. nonsmokers). In current smokers, mean baseline Q̇aw was unchanged after fluticasone treatment, but endothelium-dependent Q̇aw reactivity significantly increased to 34.9%. Q̇aw reactivity was again blunted after fluticasone washout. Endothelial dysfunction, as assessed by vascular reactivity, can be corrected with an inhaled corticosteroid in the airway of lung-healthy current smokers. This proof of concept can serve as the basis for future clinical investigations on the effect of glucocorticoids on endothelial function in smokers.

Effect of Estrogen Replacement Therapy on Endothelial Function of Peripheral Resistance Artery in Postmenopausal Women - Comparison of Normotensive Subjects and Hypertensive Patients -

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 713-713
Author(s):  
Yukihito Higashi ◽  
Mitsuhiro Sanada ◽  
Shota Sasaki ◽  
Keigo Nakagawa ◽  
Koso Ohama ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Replacement Therapy ◽  
Postmenopausal Women ◽  
Estrogen Replacement Therapy ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Sublingual Nitroglycerin ◽  
Estrogen Replacement

P112 To determine whether endothelial dysfunction is demonstrable in the forearm circulation of hypertensive postmenopausal women (HPW) compared with normotensive postmenopausal women (NPW), and to evaluate the effects of long-term estrogen replacement therapy (ERT) on endothelial function in the HPW and NPW, we randomized both HPW and NPW into groups with ERT for 12 weeks (n=26 and 10) or with placebo (n=8 and 6), respectively. Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test endothelium-dependent vasodilation, and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Basal forearm blood flow was similar in NPW and HPW. Forearm blood flow in HPW during reactive hyperemia was significantly less than that in NPW. Increases in forearm blood flow after nitroglycerin were similar in the two groups. ERT lowered LDL cholesterol and increased estradiol and HDL cholesterol; no change occurred in the placebo group. Changes in these parameters evoked by ERT were similar in HPW and NPW. Basal blood pressures, heart rate, forearm blood flow, or body weight was not changed by ERT. After 12 weeks of ERT, maximal forearm blood flow response during reactive hyperemia increased significantly from 18.4 ± 2.6 to 28.6 ± 3.4 mL/min/100 mL tissue (p<.05) in HPW and from 26.5 ± 1.9 to 30.9 ± 3.9 mL/min/100 mL tissue (p<.05) in NPW, but it was not changed by placebo. The improvement of reactive hyperemia after ERT was significantly greater in HPW than in NPW (56 ± 8 vs. 17 ± 3%, P<.05). Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of ERT. These findings suggest that continued ERT improves endothelial dysfunction in postmenopausal women, and that HPW show endothelial dysfunction which can be improved by ERT via the mechanism other than beneficial effects on lipid metabolism.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Alterations in ET-1, not nitric oxide, in 1-week-old lambs with increased pulmonary blood flow

2003 ◽  
Vol 284 (2) ◽  
pp. H480-H490 ◽  
Author(s):  
Boaz Ovadia ◽  
Olaf Reinhartz ◽  
Robert Fitzgerald ◽  
Janine M. Bekker ◽  
Michael J. Johengen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Congenital Heart Disease ◽  
Blood Flow ◽  
Heart Disease ◽  
Endothelial Function ◽  
Pulmonary Blood Flow ◽  
Congenital Heart ◽  
Vascular Reactivity ◽  
Protein Levels ◽  
Vasodilator Response

Altered pulmonary vascular reactivity is a source of morbidity and mortality for children with congenital heart disease and increased pulmonary blood flow. Nitric oxide (NO) and endothelin (ET)-1 are important mediators of pulmonary vascular reactivity. We hypothesize that early alterations in endothelial function contribute to the altered vascular reactivity associated with congenital heart disease. The objective of this study was to characterize endothelial function in our lamb model of increased pulmonary blood flow at 1 wk of life. Eleven fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt) and were studied 7 days after delivery. The pulmonary vasodilator response to both intravenous ACh (endothelium dependent) and inhaled NO (endothelium independent) was similar in shunted and control lambs. In addition, tissue NOx, NO synthase (NOS) activity, and endothelial NOS protein levels were similar. Conversely, the vasodilator response to both ET-1 and 4Ala-ET-1 (an ETBreceptor agonist) were attenuated in shunted lambs, and tissue ET-1 concentrations were increased ( P < 0.05). Associated with these changes were an increase in ET-converting enzyme-1 protein and a decrease in ETBreceptor protein levels ( P < 0.05). These data demonstrate that increased pulmonary blood flow induces alterations in ET-1 signaling before NO signaling and suggest an early role for ET-1 in the altered vascular reactivity associated with increased pulmonary blood flow.

scholarly journals The Effect of Lower Limb Revascularization on Flow, Perfusion, and Systemic Endothelial Function: A Systematic Review

Angiology ◽  
2020 ◽  
pp. 000331972096954
Author(s):  
Pasha Normahani ◽  
Sodabeh Khosravi ◽  
Viknesh Sounderajah ◽  
Mohamed Aslam ◽  
Nigel J. Standfield ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Lower Limb ◽  
Ischemia Reperfusion ◽  
Tissue Perfusion ◽  
Current Evidence ◽  
Limb Blood Flow ◽  
Flow Perfusion ◽  
The Impact

Peripheral arterial disease (PAD) is associated with reduced lower limb blood flow and tissue perfusion. The consequent reduction in vessel wall shear stress as well as ischemia–reperfusion injury has also been associated with systemic endothelial dysfunction and inflammation. We aimed to explore the impact of lower limb revascularization on (1) lower limb blood flow, (2) tissue perfusion, and (3) systemic endothelial function. We performed a systematic literature search using the MEDLINE, Embase, and Web of Science databases. Eligible studies measured changes in lower limb blood flow, perfusion, or systemic endothelial function following revascularization for the treatment of symptomatic PAD. We found 19 eligible studies, which were limited by considerable heterogeneity. Current evidence suggests that revascularization has a positive effect on flow, perfusion, and systemic endothelial dysfunction. Any changes may take a number of weeks to become apparent. There is a need for well-designed studies to explore the association between flow, perfusion, and endothelial dysfunction.

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation

2003 ◽  
Vol 105 (6) ◽  
pp. 699-707 ◽  
Author(s):  
S. E. ANDERSSON ◽  
M.-L. EDVINSSON ◽  
L. EDVINSSON
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Reactivity ◽  
Plasma Concentrations ◽  
Vascular Risk Factors ◽  
Elderly Adults ◽  
Vascular Risk ◽  
Healthy Elderly

In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein–cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

Coronary endothelial function and spontaneous coronary artery dissection

2018 ◽  
Vol 9 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Thomas M Waterbury ◽  
Marysia S Tweet ◽  
Sharonne N Hayes ◽  
Abhiram Prasad ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Coronary Blood Flow ◽  
Reference Group ◽  
Artery Dissection ◽  
Spontaneous Coronary Artery Dissection ◽  
Coronary Artery Dissection ◽  
Function Testing

Objectives: To investigate the role of endothelial function in patients with previous spontaneous coronary artery dissection. Background: Mechanisms underlying spontaneous coronary artery dissection, including a possible contribution from endothelial dysfunction, remain poorly understood. Methods: This was a single center, retrospective study of patients with a prior spontaneous coronary artery dissection episode who underwent invasive endothelial function testing in the cardiac catheterization laboratory for evaluation of recurrent chest pain. Coronary epicardial and microvascular responses to acetylcholine, adenosine, and nitroglycerine were assessed. Findings were compared to a reference group of normal controls ( n=232). Results: A total of 10 patients with prior angiographically confirmed spontaneous coronary artery dissection were referred for coronary endothelial function testing. The median coronary flow reserve was 2.8 (interquartile range (IQR) 2.3, 3.6). The median change in coronary diameter with acetylcholine was −0.9% (IQR −23.9, 4.2). The median increase in peak coronary blood flow following acetylcholine administration was 91.4% (IQR 9.1, 105.7), which was similar to the response observed in a reference group of patients (median age 51 years, 96% women) from our laboratory with normal microvascular responses to acetylcholine: 107.4% (IQR 75.5, 165.7; P=0.20). Four patients (40%) had an abnormal microvascular response to acetylcholine, with less than a 50% increase in coronary blood flow, and all but one patient had left anterior descending artery or multivessel spontaneous coronary artery dissection. Conclusion: Coronary epicardial and microvascular vasomotor dysfunction is not a predominant feature of spontaneous coronary artery dissection. Endothelial dysfunction is not implicated as the principal underlying mechanism.

scholarly journals Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/ oxidative stress

2021 ◽  
Author(s):  
Patrizia Dardi ◽  
Laís Rossi Perazza ◽  
Gisele Kruger Couto ◽  
Gianne Paul Campos ◽  
Luciano dos Santos Aggum Capettini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Thoracic Aorta ◽  
Vascular Reactivity ◽  
Vena Cava ◽  
Coronary Artery Occlusion ◽  
H2o2 Production ◽  
No Production

Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, four weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, whilst protein expression and dimer/monomer ratio was assessed by western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared to vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, this study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.

scholarly journals Cigarette Smoking Is Related to Endothelial Dysfunction of Resistance, but Not Conduit Arteries in the General Population—Results From the Gutenberg Health Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Omar Hahad ◽  
Natalie Arnold ◽  
Jürgen H. Prochaska ◽  
Marina Panova-Noeva ◽  
Andreas Schulz ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cigarette Smoking ◽  
Endothelial Function ◽  
Smoking Status ◽  
Health Study ◽  
Computer Assisted ◽  
Resistance Arteries ◽  
Gutenberg Health Study ◽  
Quitting Smoking ◽  
Former Smokers

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction.Conclusions: Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.

Abstract 483: Mas/AT2 Receptor Deficient Mice Present A Pronounced Endothelial Dysfunction That Is Exclusively Mas-Related

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Daniel C Villela ◽  
Mihail Todiras ◽  
Thomas Unger ◽  
Natalia Alenina ◽  
Michael Bader ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Reactivity ◽  
Dose Range ◽  
Renin Angiotensin System ◽  
At2 Receptor ◽  
Double Knockout ◽  
Vasodilatory Response ◽  
Significant Difference

The angiotensin type 2 (AT2) receptor and the angiotensin-(1-7) receptor MAS belong to the protective arm of the Renin Angiotensin System (RAS). They behave in a very similar way in terms of their physiological (tissue-protective) actions. Here we evaluate the endothelial function of Mas/AT2 double knockout mice (DKO) in two different backgrounds, C57BL/6 and FVB/N-C57BL/6 mixed background. Endothelial function in conscious mice was evaluated by measuring changes in mean arterial pressure (MAP) in response to bolus intra-aortic acetylcholine (ACh) and sodium nitroprusside (SNP) administration. The substances were given in 1μL per 10 g of body weight at the following doses: 25, 50, 100 ng/kg for ACh and 10 μg/kg for SNP. To correct the differences in vascular smooth muscle reactivity, the response to ACh was normalized by the SNP response. Our main results show that regarding the absolute response to ACh, Mas/AT2 DKO animals in both backgrounds had markedly decreased vasodilation response when compared with wild type (WT) over the dose range of 25 to 100 ng/kg (table 1). The MasKO animals had similar impairment of the vasodilatory response as the DKO mice when compared with WT animals, thus there was no statistical difference between the MasKO and DKO animals. No significant difference between the AT2KO and WT animals was observed in regard to the vasodilatory response to ACh. Normalization of ACh response with the SNP effect reinforced the observation that endothelium-dependent vascular reactivity was impaired. The evidence provided in this study suggests that the endothelial dysfunction observed in the Mas/AT2 DKO animals is exclusively due to the deletion of Mas.

Abstract 55: Hiv Viral Proteins Elevate Blood Pressure And Impairs Endothelial Function In Resistance Arteries Via Sex Specific, Immune And Nox1-dependent Mechanisms In Mice.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Taylor Kress
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Viral Infection ◽  
Immune Cells ◽  
Vascular Reactivity ◽  
Radio Telemetry ◽  
Viral Proteins ◽  
Mesenteric Arteries ◽  
Resistance Arteries

Thanks to the onset of combination antiretroviral therapy (cART), patients living with HIV live longer but experience accelerated rates of hypertension. However, the etiology of HIV-associated hypertension remains ill defined, specifically the respective contributions of repressed viral infection and cART treatment. Herein, we took advantage of a transgenic model (Tg26) of repressed viral infection to investigate the contribution of HIV viral proteins to hypertension. Quantification of inflammatory cytokines revealed elevated circulating TNFα levels but also high aorta and intraperitoneal immune cells TNFα in male Tg26 mice leading to the hypothesis that HIV-associated hypertension involves immune-derived TNFα secretion and endothelial dysfunction in males and females Tg26 mice. Blood pressure (BP) was measured via radio telemetry and vascular reactivity studies performed via wire myography. BP analysis revealed increased mean arterial pressure (MAP: male: WT=112.3±1.3 vs Tg26=121.9±4.0 mmHg/ female: WT=110.6±3.01/ Tg26=120.3±6.9 mmHg) and heart rate in both sexes (P<0.05). However, blockade of TNFα action with etanercept restored BP and aortic endothelial function in male Tg26 mice only. Along with an increase in TNFα, male Tg26 aortas showed infiltration of Tcells and proinflammatory cytokines IL-18, and IL-6, which were not seen in females. However, scavenging of reactive oxygen species with the selective NOX1 inhibitor GKT771 restored aorta endothelial function in both sexes. A contributor to hypertension is impaired endothelial relaxation in resistance arteries. Mesenteric arteries showed impaired endothelial relaxation to acetylcholine in both male and female Tg26 mice (P<0.05) with no impairment in smooth muscle cell relaxation. This phenotype was reproduced in WT mice transplanted with Tg26 bone marrow (BM) and remarkably reversed in Tg26 mice receiving WT BM supporting a clear role for immune cells in endothelial dysfunction. Collectively, these data indicate that HIV-related hypertension involves immune and NOX1-dependent endothelial dysfunction in both sexes but TNFα-dependent mechanisms in males only providing evidence of sex specific mechanisms.

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