Nadir blood pressure responses to longer consecutive cardiac cycle sequences absent of sympathetic bursts are associated with popliteal endothelial-dependent dilation.

PURPOSE: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP. METHODS: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined. RESULTS: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72). CONCLUSION: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA.

Impact of unilateral dual-brachial arteries on endothelial-dependent and endothelial-independent vasodilation: a case study.

TAKE HOME MESSAGE: Our case study indicated that a bifurcated brachial artery exhibited worse vasodilatory responses relative to an intact contralateral artery.

An acute bout of prolonged sitting blunts popliteal endothelium-independent dilation in young, healthy adults.

A single bout of prolonged uninterrupted sitting increases oxidative stress, reduces popliteal blood flow-induced shear stress, and diminishes endothelium-dependent, flow-mediated dilation (FMD). The FMD response is also influenced by the sensitivity of vascular smooth muscle cells to nitric oxide (i.e., endothelium-independent dilation), which is also attenuated by elevated oxidative stress. However, it is currently unknown whether prolonged sitting impacts popliteal endothelium-independent dilation responses, which may uncover a novel mechanism associated with sitting-induced vascular dysfunction. This study tested the hypothesis that prolonged sitting attenuates both popliteal FMD and endothelium-independent, nitroglycerin-mediated dilation responses (NMD, 0.4 mg sublingual dose). Popliteal blood flow (mL/min), relative FMD (%), and NMD (%) were assessed via duplex ultrasonography before and after a ∼3-h bout of sitting in 14 young, healthy adults (8♀; 22 ± 2 yr). Prolonged sitting attenuated resting blood flow (57 ± 23 to 32 ± 16 mL/min, P < 0.001), relative FMD (4.6 ± 2.8% to 2.2 ± 2.5%; P = 0.001), and NMD (7.3 ± 4.0% to 4.6 ± 3.0%; P = 0.002). These novel findings demonstrate that both endothelium-dependent and independent mechanisms contribute to the adverse vascular consequences associated with prolonged bouts of sitting.NEW & NOTEWORTHY We demonstrate that lower-limb vascular smooth muscle function is attenuated in young, healthy adults after an acute bout of prolonged sitting. These data indicate that prolonged sitting-induced vascular dysfunction involves both endothelium-dependent and -independent mechanisms.

Impact of the Post-Thrombotic Syndrome on the Arterial Wall of the Lower Limbs.

OBJECTIVE: Deep vein thrombosis of the lower limbs is a common disease in vascular surgery. Approximately 20-50% of deep vein thrombosis patients develop post-thrombotic syndrome, which can severely affect the patient's quality of life. However, the precise science of the pathophysiology of the progression of the post-thrombotic syndrome remains unclear. Studies have demonstrated that patients with post-thrombotic syndrome of the lower limbs have impaired arterial wall endothelial function. Nevertheless, there is little research on the different impacts of post-thrombotic syndrome on the arterial wall endothelial function between the affected limbs and the healthy limbs. This study aims to assess this difference. METHODS: A total of 60 patients treated for the post-thrombotic syndrome of the lower limbs were included. The flow-mediated dilation (FMD%) and nitroglycerin-mediated dilation (NMD%) were measured to assess the different endothelial function alterations of the common femoral arterial wall between the affected limb and the healthy limb. RESULTS: No significant differences in the common femoral artery diameter between the affected limbs and the healthy limbs were discovered (8.94 ± 0.92 mm vs 8.75 ± 1.0 mm, P = 0.710). The flow-mediated dilation of the common femoral artery of the affected limbs were significantly lower compared to the healthy limbs (FMD%: 3.21 ± 1.07% vs 5.19 ± 1.35%, P = 0.001). However, there was no significant difference in the nitroglycerin-mediated dilation of the common femoral artery between the affected limbs and the healthy limbs（ NMD%: 13.37 ± 1.78% versus 14.45 ± 2.14%, P = 0.083). CONCLUSIONS: Our results demonstrated the association between post-thrombotic syndrome and deteriorated endothelial functional properties of the arterial wall of the lower limbs. Endothelial dysfunction of the arteries wall was more severe in the affected lower limbs with the post-thrombotic syndrome than in the healthy limbs. The mentioned findings may partly explain the pathophysiology of the progression post-thrombotic syndrome of the lower limbs. HIGHLIGHTS: tudies have demonstrated that patients with post-thrombotic syndrome of the lower limbs have impaired arterial wall endothelial function. Our results demonstrated the endothelial dysfunction of the arteries wall was more severe in the affected lower limbs with the post-thrombotic syndrome than in the healthy limbs. Our findings may partly explain the pathophysiology of the progression post-thrombotic syndrome of the lower limbs.

Endothelial Dysfunction and Atherosclerosis in Patients With Autosomal Dominant Polycystic Kidney Disease.

Introduction In this study, we aimed to determine the endothelial dysfunction (ED) and atherosclerosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and methods This study was conducted with 83 subjects (26 male, mean age: 46±11 years) consisted of three groups including ADPKD, hypertension (HT) and healthy control groups. The groups were evaluated in terms of serum endocan and asymmetric dimethylarginine (ADMA) levels, flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD) and carotid intima-media thickness (CIMT). Results Serum endocan and ADMA levels and CIMT were significantly higher while NMD was significantly lower in ADPKD group than control group. FMD and NMD were lower but serum ADMA level was higher in the ADPKD group than HT group; while serum endocan level and CIMT were not significantly different in ADPKD and HT groups. In ADPKD patients, CIMT value and serum endocan and ADMA levels were higher while NMD was lower in patients with eGFR≤60 mL/min/1.73 m2 than patients with eGFR>60 mL/min/1.73 m2. Serum ADMA level was higher and NMD was lower in hypertensive ADPKD patients than non-hypertensive ones. Serum endocan level was higher in ADPKD patients with nephrolithiasis and a negative correlation was detected between serum endocan level and 24-hour urine volume. Conclusions Endothelial dysfunction and atherosclerosis are common conditions in ADPKD patients and it was further reinforced in our study. In order to clarify the relationship between serum endocan level and 24-hour urine volume, which is a remarkable finding in our study, larger studies that including the measurement of urine endocan may be useful.

The impact of age and sex on popliteal artery endothelial-dependent vasodilator and vasoconstrictor function.

Lower-limb arteries, such as the popliteal artery, are a common site of atherosclerosis. These arteries are habitually exposed to large fluctuations in blood flow during physical and sedentary activities. Low-flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) provide indices of endothelial-dependent vasoconstriction and vasodilation, respectively. Age and sex both impact upper-limb FMD. However, it is unclear whether these factors also influence popliteal endothelial-dependent function. Popliteal endothelial function was compared between younger and older males and females (n=14 per group) matched for age- and sex-specific relative aerobic fitness levels (each group's normative percentile: ~45%). Nitroglycerin-mediated dilation (NMD) was also assessed as a measure of endothelial-independent vasodilation. Ageing reduced relative popliteal FMD in both males (older: 4.3±1.8% versus younger 5.7±1.9%) and females (older: 2.9±1.8% versus younger: 6.1±1.6%, both: P<0.046). FMD was also lower in older females versus older males (P=0.04). Popliteal NMD findings followed the same pattern as FMD. Compared to younger adults, relative L-FMC responses were blunted among older males (older: -1.2±1.1% versus younger: -2.2±1.0%) and females (older: -1.0±1.2% versus younger: -2.1±1.3%, both P<0.03) with no sex-differences observed in either age group (all, P>0.60). The adverse age- and sex-related (older adults only) declines in popliteal FMD were mediated, in part, by reduced vascular smooth muscle sensitivity to nitric oxide. Endothelial-dependent vasoconstriction was also attenuated with age, but unaffected by sex. Despite similar normative aerobic fitness percentiles (~45%), older adults exhibited attenuated popliteal endothelial function than their younger counterparts. This was particularly evident in older females who exhibited the lowest endothelial-dependent vasodilatory responses.

Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.

Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects.

BACKGROUND: The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by noninvasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions. Endothelial function is also involved in growth and proliferation of tumor cells. METHODS: We performed a literature review and assessed the role of the natural polyphenol, curcumin, as a potential inexpensive, well-tolerated, and safe agent for improving endothelial function. RESULTS: Curcumin exerts several positive pharmacological effects; these include anti-inflammatory, antioxidant, anti-hypertensive, anti-cancer, antiviral, anti-infective and wound-healing properties. Specifically, curcumin's anti-inflammatory effects are thought to be caused by reducing trans-endothelial monocyte migration by reduction of mRNA and protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin and by modulating NFκB, JNK, p38 and STAT-3 in endothelial cells. Dietary curcumin supplementation can also increase antioxidant activity through the induction of heme oxygenase-1, a scavenger of free radicals, and by reduction of reactive oxygen species and Nox-2. CONCLUSIONS: Curcumin appears to improve endothelial function but additional research is needed to determine the precise mechanism(s) and biomarkers involved in curcumin's therapeutic effects on endothelial dysfunction.

Medicinal Plants Targeting Cardiovascular Diseases in View of Avicenna.

BACKGROUND: Cardiovascular disease (CVD) is a spectrum of diseases involving the heart and blood vessels, and the first cause of mortality worldwide. Medicinal plants have been used for thousands of years to treat CVD. In Traditional Persian Medicine (TPM), there is a special focus on heart diseases. Avicenna, a Persian physician of the eleventh century compiled a book devoted to this field named "The treatise on cardiac drugs" which is a compendium of TPM knowledge on CVD. Avicenna mentioned 50 cardiovascular active plants and described their therapeutic effects in the treatment of CVDs. METHODS: Here, we perform a detailed search in scientific databases to verify the cardiovascular activities of the medicinal plants suggested by Avicenna. Also, we discussed cardiovascular activities of a number of the most important suggested plants as well as their efficacy in clinical studies. Major bioactive compounds identified from these plants are also discussed. RESULTS: Pharmacological studies have revealed that the majority of these plants are effective in cardiovascular health with various mechanisms. Among them, Crocus sativus L., Cinnamomum cassia (L.) J. Presl, Punica granatum L., Ocimum basilicum L., Elettaria cardamomum (L.) Maton, Melissa officinalis L. and Phyllanthus emblica L. have proved to be more effective. CONCLUSION: The above-mentioned plants can be rich sources for developing new and effective pharmaceuticals for the treatment of CVDs.

Effect of Long-Term Administration of Nicorandil on Endothelial Function of the Radial Artery in Patients With Angina Undergoing Transradial Percutaneous Coronary Intervention.

We evaluated the effect of long-term administration of nicorandil on endothelial function of the radial artery in patients with angina undergoing elective transradial coronary intervention (TRI). A total of 127 patients were randomly assigned to nicorandil (standard medication plus nicorandil 5 mg twice daily, n = 64) or control group (standard medication except nicorandil, n = 63) immediately after TRI procedure. Radial artery diameter (RAD), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) of radial artery were measured 1 day before TRI as well as 1 day and 3 months after TRI by Ultrasound-Doppler. No significant difference was observed in the baseline RAD, FMD, and NMD between the 2 groups (all P > .05). In cannulated arm, at 3-month follow-up, RAD in nicorandil group was much larger than that in the control group (2.78 ± 0.27 mm vs 2.61 ± 0.30 mm, P = .001). Besides, FMD and NMD were much higher in nicorandil group than those in the control group (10.38% ± 2.43% vs 6.81% ± 1.86%; 15.94% ± 6.28% vs 10.46% ± 5.37%, respectively, all Ps < .001). In conclusion, long-term administration of nicorandil after TRI could improve the endothelial function of the cannulated radial artery.

Vascular Function at Baseline in the Hemodialysis Fistula Maturation Study.

BACKGROUND: End-stage renal disease is accompanied by functional and structural vascular abnormalities. The objective of this study was to characterize vascular function in a large cohort of patients with end-stage renal disease, using noninvasive physiological measurements, and to correlate function with demographic and clinical factors. METHODS AND RESULTS: We analyzed cross-sectional baseline data from the Hemodialysis Fistula Maturation Study, a multicenter prospective observational cohort study of 602 patients with end-stage renal disease from 7 centers. Brachial artery flow- and nitroglycerin-mediated dilation, carotid-femoral and -radial pulse wave velocity, and venous occlusion plethysmography were performed prior to arteriovenous fistula creation. Relationships of these vascular function measures with demographic, clinical, and laboratory factors were evaluated using linear mixed-effects models. Arterial function, as assessed by flow- and nitroglycerin-mediated dilation and carotid-femoral pulse wave velocity, worsened with increasing age and diabetes mellitus. Venous capacitance decreased with diabetes mellitus but not with age. Flow-mediated dilation was higher among patients undergoing maintenance dialysis than for those at predialysis, and a U-shaped relationship between serum phosphorus concentration and flow-mediated dilation was evident. Partial correlations among different measures of vascular function, adjusting for demographic factors, diabetes mellitus, and clinical center, were modest or essentially nonexistent. CONCLUSIONS: Multiple demographic and clinical factors were associated with the functions of vessels of different sizes and types in this large cohort of patients with end-stage renal disease. Low correlations between the different measures, controlling for demographic factors, diabetes mellitus, and center, indicated that these different types of vascular function otherwise vary heterogeneously across patients.

Impact of transradial coronary procedures on radial artery function.

We evaluated the impact of transradial coronary procedures on the vasodilatory function of the radial artery. A total of 65 patients who underwent transradial coronary procedures were enrolled. All patients were examined with B-mode high-resolution ultrasound. Radial artery baseline diameter and response to flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) were measured in the right radial artery. The FMD of the right radial artery was 11.5%, 4.1%, and 0.7%, respectively, before the procedures, 1 day, and 3 months after the procedures (P < .05 at 1 day, P < .01 at 3 months). The NMD of the right radial artery was 17.6%, 5.4%, and 6.3%, respectively, before the procedures, 1 day, and 3 months after the procedures (P < .05 at 1 day, P < .05 at 3 months). Transradial coronary procedures decrease radial artery FMD and NMD resulting in immediate and persistent blunting of vasodilatory function.