Abstract 089: CD36 Genetic Variant Impacts Nitric Oxide Regulation of Endothelial Function: Response to Chronic Treatment with Phosphodiesterase 5 Inhibition

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Cyndya A Shibao ◽  
Jorge E Celedonio ◽  
Latisha Gregory-Love ◽  
Claudia E Ramirez ◽  
Amy C Arnold ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Chronic Treatment ◽  
Genetic Variant ◽  
Sildenafil Citrate ◽  
Flow Mediated Dilation ◽  
Fasting Insulin ◽  
The Mean ◽  
Phosphodiesterase 5

CD36, a scavenger receptor expressed on endothelial cells, interacts with thrombospodin-1, a matrix protein that modulates nitric oxide-soluble guanylate cyclase (NO-sGC) signaling. CD36 genetic variants associate with endothelial dysfunction, atherosclerosis, hypertension and insulin resistance. A coding variant of CD36 (rs3211938, G/T genotype) that causes partial CD36 deficiency (50% reduction) is common (~18%) in African Americans (AA); however, it is unknown, if this genotype influences NO-dependent endothelial function. This study examined whether potentiating NO-sGC pathways with the phosphodiesterase 5 inhibitor, sildenafil citrate, improves endothelial function and insulin sensitivity in AA women with or without the G/T genotype. Forty-six AA women with metabolic syndrome (MetS) participated in a 4-week, parallel-arm, double-blind, and placebo-controlled study. Carefully matched subjects were randomly assigned to sildenafil citrate 20 mg TID versus placebo; sildenafil (n= 23, 42±10 years old, BMI 39±5 kg/m2, fasting insulin 15±8 uU/ml) and placebo (n=23, age 43±10, BMI 39±6 kg/m2, fasting insulin 14±10 uU/ml). Primary endpoints were insulin sensitivity and endothelial function measured by intravenous glucose tolerance test and flow mediated dilation, respectively. Treatment compliance was documented with plasma sildenafil levels (mean 57±50 ng/ml). There was no difference in insulin sensitivity (p=0.676) or flow-mediated dilation (p=0.649) between intervention groups. However, subgroup analyses showed a significant interaction between sildenafil citrate treatment and G/T genotype (p=0.018). Sildenafil citrate improved endothelial function in G/T carriers (the mean difference: 2.9, the 95% CI: -0.90 to 6.8, p = 0.126) and decreased endothelial function in T/T carriers (the mean difference: -2.6, the 95% CI: -5.1 to -0.1, p = 0.040). We conclude that the rs3211938 common CD36 genetic variant influences NO-dependent endothelial function in response to chronic treatment with phosphodiesterase 5 inhibition. Further studies are needed to determine if rs3211938 and other common CD36 genotypes influence endothelial function and the inter-individual variability in response to the drug.

scholarly journals The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727)

2017 ◽  
Vol 55 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Morteza Safi ◽  
Mohammad Parsa Mahjoob ◽  
Saeed Nateghi ◽  
Isa Khaheshi ◽  
Mohammad Ali Akbarzadeh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clinical Trial ◽  
Endothelial Function ◽  
Term Effect ◽  
Flow Mediated Dilation ◽  
Placebo Administration ◽  
Short Term ◽  
The Mean ◽  
Artery Disease

Abstract Background. Recent studies have confirmed the essential and paramount role of the L-Citrulline on the nitric oxide regulation and the endothelial function improvement. Materials and Methods. In this cross-over clinical trial, thirty patients, diagnosed with coronary artery disease (CAD) and flow mediated dilation to nitroglycerin dependent vasodilation (FMD/NMD) ratio less than 1, were included. The patients were randomly divided into two groups of 15 patients and underwent treatment by L-Citrulline or placebo for 15 days, in 2 step protocol. The indicators of assessment in the current study were the ratio of the FMD/NMD and FMD value. Results. In the current cross-over clinical trial, the mean of FMD to NMD ratio and mean FMD value of all patients before starting the protocol were 0.91 ± 0.08 and 4.04 ± 0.51 mm, respectively. The final results of study showed that following L-Citrulline administration, mean FMD to NMD ratio and mean FMD value were enhanced to: 1.03 ± 0.09 and 4.96 ± 0.72 mm, respectively, which were statistically significant (P<0.001 and P<0.001, respectively). However, following placebo administration, mean FMD to NMD ratio and mean FMD value were receded to: 0.92 ± 0.09 and 4.06 ± 0.22 mm, respectively, which were not statistically significant (P = 0.75 and P = 0.89, respectively). Moreover, the improvement of mean FMD to NMD ratio (0.12 ± 0.02) and mean FMD value (0.92 ± 0.16 mm), following L-Citrulline administration, were statistically significant in comparison with the change of mean FMD to NMD ratio (0.01 ± 0.002) and mean FMD value (0.02 ± 0.003), following placebo administration (P<0.001 and P<0.001, respectively). Conclusion. L-Citrulline treatment can lead to improvement of the endothelial function in patients diagnosed with CAD which are assessed via FMD to NMD ratio FMD value enhancements.

scholarly journals A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition

2016 ◽  
Vol 101 (7) ◽  
pp. 2751-2758 ◽  
Author(s):  
Cyndya A. Shibao ◽  
Jorge E. Celedonio ◽  
Claudia E. Ramirez ◽  
Latisha Love-Gregory ◽  
Amy C. Arnold ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Controlled Trial ◽  
Scavenger Receptor ◽  
Response To Treatment ◽  
Flow Mediated Dilation ◽  
Endothelial Nitric Oxide ◽  
Phosphodiesterase 5

Context: The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction. Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences endothelial function, insulin sensitivity (IS), and the response to treatment with the nitric oxide-cGMP potentiator sildenafil. Design: IS (frequently sampled iv glucose tolerance) and endothelial function (flow mediated dilation [FMD]) were determined in age- and body mass index-matched obese AA women with or without the G allele of rs3211938 (protocol 1). Effect of chronic sildenafil treatment on IS and FMD was tested in AA women with metabolic syndrome and with/without the CD36 variant, using a randomized, placebo-controlled trial (protocol 2). Setting: Two-center study. Participants: Obese AA women. Intervention: A total of 20-mg sildenafil citrate or placebo thrice daily for 4 weeks. Main outcome: IS, FMD. Results: G allele carriers have lower FMD (P = .03) and cGMP levels (P = .01) than noncarriers. Sildenafil did not improve IS, mean difference 0.12 (95% confidence interval [CI], −0.33 to 0.58; P = .550). However, there was a significant interaction between FMD response to sildenafil and rs3211938 (P = .018). FMD tended to improve in G carriers, 2.9 (95% CI, −0.9 to 6.8; P = .126), whereas it deteriorated in noncarriers, −2.6 (95% CI, −5.1 to −0.1; P = .04). Conclusions: The data document influence of a common genetic variant on susceptibility to endothelial dysfunction and its response to sildenafil treatment.

Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function

2005 ◽  
Vol 99 (4) ◽  
pp. 1621-1621 ◽  
Author(s):  
Clare E. Austin
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

Flow-mediated dilatation revisited

2005 ◽  
Vol 99 (4) ◽  
pp. 1623-1623 ◽  
Author(s):  
Robinson Joannides ◽  
Jeremy Bellien
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
Flow Mediated Dilatation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

scholarly journals Study of endothelial function in pregnant women with gestational diabetes mellitus by flow mediated dilation of brachial artery

2020 ◽  
Vol 9 (6) ◽  
pp. 2377
Author(s):  
Nidhi Pandey ◽  
Poonam Goel ◽  
Anita Malhotra ◽  
Reeti Mehra ◽  
Navjot Kaur
Keyword(s):  
Gestational Diabetes ◽  
Endothelial Function ◽  
Pregnant Women ◽  
Brachial Artery ◽  
Vascular Function ◽  
Post Partum ◽  
Control Group ◽  
Flow Mediated Dilation ◽  
The Mean ◽  
The Difference

Background: The objective of the study was to assess vascular function in normal pregnant women and women with gestational diabetes and to study its temporal relationship with gestational age at 24-28-week POG and at 36-38-week POG and changes in FMD in postpartum period.Methods: Assessment of vascular function was done at 24-28-week POG, 36-38-week POG and at 6-12-week postpartum by flow mediated dilation of brachial artery in 37 healthy pregnant women and 37 pregnant women with GDM.Results: In GDM group mean FMD at 24-28 weeks of POG, at 36-38 weeks POG was lower as compared to the control group (11.225±6.20,8.464±6.09 versus 14.49±5.21, 10.898±4.12) although the difference in mean FMD in two groups was not statistically significant. It was found that the decrease in FMD at 36-38-week POG as compared to 24-28 weeks POG was statistically significant in both the groups (p<0.001).Conclusions: This study revealed that when endothelial function as assessed by FMD was compared at different period of gestation, the mean decrease in FMD at 36-38-week POG as compared to 24-28-week POG and 6-week post-partum was statistically significant in patients with GDM and as well as the control group, however this trend of change was same in both the groups and was not statistically significant when compared between the two group (GDM versus control). A negative correlation of FMD was found with BMI, and HBA1c, that was stronger in GDM group.

FMD vs. pharmacological approaches for endothelial function

2005 ◽  
Vol 99 (4) ◽  
pp. 1627-1627
Author(s):  
Hirofumi Tanaka
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

Flow-mediated dilation analysis coupled with nitric oxide transport to enhance the assessment of endothelial function

2021 ◽  
Author(s):  
Tianxiang Ma ◽  
Xiao Liu ◽  
Quan Ren ◽  
Zhexi Zhang ◽  
Xiaoning Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Endothelial Function ◽  
Characteristic Parameter ◽  
Flow Mediated Dilation ◽  
Fractional Flow ◽  
Arterial Diameter ◽  
Brachial Artery Diameter ◽  
Significant Difference

Flow-mediated dilation (FMD), mainly mediated by nitric oxide (NO), aims to assess the shear-induced endothelial function, which is widely quantified by the relative change in arterial diameter after dilation (FMD%). However, FMD% is affected by individual differences in blood pressure, blood flow and arterial diameter. To reduce these differences and enhance the assessment of FMD to endothelial function, we continuously measured not only the brachial artery diameter and blood flow with ultrasound but also blood pressure with non-invasive monitor during standard FMD test. We further constructed an analytical model of FMD coupled with NO transport, blood flow, and arterial deformation. Combining the time-averaged and peak values of arterial diameter, blood flow and pressure, and the modeling, we assumed the artery was completely healthy and calculated an ideally expected FMD% (eFMD%). Then, we expressed the fractional flow-mediated dilation (FFMD%) for the ratio of measured FMD% (mFMD%) to eFMD%. Furthermore, using the continuous waveforms of arterial diameter, blood flow and pressure, the endothelial characteristic parameter (ϵ) was calculated, which describes the function of the endothelium to produce NO and ranges from 1 to 0 representing the endothelial function from healthiness to complete loss. We found that the mFMD% and eFMD% between the young age (n=5, 21.2±1.8yr) and middle age group (n=5, 34.0±2.1yr) have no significant difference (P=0.222, P=0.385). In contrast, the FFMD% (P=0.008) and ϵ (P=0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (ϵ) may have the potential for specifically diagnosing the endothelial function.

Abstract 3119: Insulin Resistance is Associated with Impaired Flow-mediated Vasodilatation in a Multi-ethnic Population: The Northern Manhattan Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takuya Hasegawa ◽  
Marco R Di Tullio ◽  
Bernadette Boden-Albala ◽  
Zhezhen Jin ◽  
Mitchell S Elkind ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Function ◽  
Rhode Island ◽  
Fasting Glucose ◽  
Reactive Hyperemia ◽  
Density Lipoprotein ◽  
Fasting Insulin ◽  
Normal Fasting Glucose ◽  
The Mean ◽  
Race Ethnicity

Background: Metabolic abnormalities, including diabetes mellitus, are associated with impaired endothelial function. However, the relationship between endothelial function and glucose metabolism has not been thoroughly investigated. Aim: We tested the hypothesis that insulin resistance is associated with impaired flow-mediated vasodilatation (FMD) in a population-based multi-ethnic cohort. Methods: As part of the Northern Manhattan Study, we measured fasting insulin levels and FMD during reactive hyperemia by high-resolution ultrasonography in 601 community participants without diabetes. General linear models were used to test the association of fasting insulin, as a surrogate maker of insulin resistance (IR), with FMD after adjusting for age, sex, race-ethnicity, waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, smoking, and fasting glucose. Mean FMD was also compared among the following three subgroups: normal fasting glucose (NFG) with IR (NFG*IR+), NFG without IR (NFG*IR−), and impaired fasting glucose (IFG). IR was defined as the upper quartile of homeostasis model index of insulin resistance (HOMA-IR). Results: The mean age was 66±9 years; 43% were male, 15% white, 16% black, and 68% Hispanic. The mean HOMA-IR was 2.45±1.88. In multiple linear regression analyses, fasting insulin was inversely correlated with FMD (β= −0.05, SE=0.02, p=0.032), after adjustment for other covariates. Race-ethnicity was not a significant modifier of the association of fasting insulin with FMD. The mean FMD was greatest in NFG*IR− even after adjustment [FMD (95% CI) 6.28 (5.91– 6.64) for NFG*IR−, 5.21 (4.43–5.99) for NFG*IR+, and 5.04 (4.33–5.74) for IFG (p<0.001)]. Conclusion: Insulin resistance was independently associated with impaired FMD. The impairment of FMD was also observed in subjects with insulin resistance even in the presence of normal fasting glucose. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont). Multivariate analysis of association of FMD with demographic and clinical variables

scholarly journals Blue light exposure decreases systolic blood pressure, arterial stiffness, and improves endothelial function in humans

2018 ◽  
Vol 25 (17) ◽  
pp. 1875-1883 ◽  
Author(s):  
Manuel Stern ◽  
Melanie Broja ◽  
Roberto Sansone ◽  
Michael Gröne ◽  
Simon S Skene ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Function ◽  
Blue Light ◽  
Pulse Wave ◽  
Light Exposure ◽  
Nitroso Compounds ◽  
Whole Body ◽  
Flow Mediated Dilation ◽  
Forearm Vascular Resistance

Aims Previous studies have shown that ultraviolet light can lead to the release of nitric oxide from the skin and decrease blood pressure. In contrast to visible light the local application of ultraviolet light bears a cancerogenic risk. Here, we investigated whether whole body exposure to visible blue light can also decrease blood pressure and increase endothelial function in healthy subjects. Methods In a randomised crossover study, 14 healthy male subjects were exposed on 2 days to monochromatic blue light or blue light with a filter foil (control light) over 30 minutes. We measured blood pressure (primary endpoint), heart rate, forearm vascular resistance, forearm blood flow, endothelial function (flow-mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite and nitroso compounds (secondary endpoints) during and up to 2 hours after exposure. Results Blue light exposure significantly decreased systolic blood pressure and increased heart rate as compared to control. In parallel, blue light significantly increased forearm blood flow, flow-mediated dilation, circulating nitric oxide species and nitroso compounds while it decreased forearm vascular resistance and pulse wave velocity. Conclusion Whole body irradiation with visible blue light at real world doses improves blood pressure, endothelial function and arterial stiffness by nitric oxide released from photolabile intracutanous nitric oxide metabolites into circulating blood.

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