Assessment of the endothelial function with changed volume of brachial artery by menstrual cycle.

BACKGROUND: The endothelial function has been proven to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. The flow-mediated vasodilation (FMD) of the peripheral artery is an endothelium-dependent function. Brachial-artery ultrasound scanning is the popular method for evaluating FMD. However, good technical training on ultrasonography is required for the user to obtain high-quality data. Therefore, the goal of this study was to propose a new method which only used a sphygmomanometer cuff to occlude the blood flow and record the vascular volume waveform (Vwave). RESULTS: We used this method to assess the FMD in the menstrual cycle for 26 volunteer females. All female subjects were evaluated two times (M: menstrual phase; F: luteal phase) in one menstrual cycle and for two cycles. In the first cycle, the FMD volume ratio in M was 101.9 ± 45.5 % and was higher in L, at 137.5 ± 62.1 % (p = 0.0032 versus M). In the second cycle, the FMD volume ratios in M and L were 91.4 ± 37.0 % and 124.0 ± 56.4 %, respectively (p < 0.001 vs. M). CONCLUSIONS: Our results have confirmed those results in the study of Hametner et al. Blood pressure measurement and FMD assessment all used the same mechanic of digital blood pressure monitor, which makes our method suitable using at home.

Characterization of Pax3-expressing cells from adult blood vessels.

We report expression of Pax3, an important regulator of skeletal muscle stem cell behaviour, in the brachial and femoral arteries of adult mice. In these contractile arteries of the limb, but not in the elastic arteries of the trunk, bands of GFP-positive cells were observed in Pax3(GFP/+) mice. Histological and biochemical examination of the vessels, together with clonal analysis after purification of Pax3-GFP-positive cells by flow cytometry, established their vascular smooth muscle identity. These blood-vessel-derived cells do not respond to inducers of other mesodermal cell types, such as bone, however, they can contribute to muscle fibre formation when co-cultured with skeletal muscle cells. This myogenic conversion depends on the expression of Pax3, but is rare and non-cell autonomous as it requires cell fusion. Myocardin, which promotes acquisition of a mature smooth muscle phenotype in these Pax3-GFP-positive cells, antagonises their potential for skeletal muscle differentiation. Genetic manipulation shows that myocardin is, however, positively regulated by Pax3, unlike genes for other myocardin-related factors, MRTFA, MRTFB or SRF. Expression of Pax3 overlaps with that reported for Msx2, which is required for smooth muscle differentiation of blood vessel-derived multipotent mesoangioblasts. These observations are discussed with respect to the origin and function of Pax3-expressing cells in blood vessels, and more general questions of cell fate determination and adult cell plasticity and reprogramming.

Habitually exercising older men do not demonstrate age-associated vascular endothelial oxidative stress.

We tested the hypothesis that older men who perform habitual aerobic exercise do not demonstrate age-associated vascular endothelial oxidative stress compared with their sedentary peers. Older exercising men (n=13, 62±2 years) had higher (P<0.05) physical activity (79±7 vs. 30±6 MET hours per week) and maximal exercise oxygen consumption (42±1 vs. 29±1 mL kg(-1) per minute) vs. sedentary men (n=28, 63±1 years). Brachial artery flow-mediated dilation (FMD), a measure of vascular endothelial function, was greater (P<0.05) in the exercising vs. sedentary older men (6.3±0.5 vs. 4.9±0.4%Δ) and not different than young controls (n=20, 25±1 years, 7.1±0.5%Δ). In vascular endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38±0.06 vs. 0.77±0.10 AU). This was associated with lower endothelial expression of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47(phox) subunit, 0.33±0.05 vs. 0.61±0.09 AU) and the redox-sensitive transcription factor nuclear factor kappa B (NFκB) (p65 subunit, 0.36±0.05 vs. 0.72±0.09 AU). Expression of the antioxidant enzyme manganese superoxide dismutase (SOD) (0.57±0.13 vs. 0.30±0.04 AU) and activity of endothelium-bound extracellular SOD were greater (6.4±0.5 vs. 5.0±0.6 U mL(-1) per minute) in the exercising men (both P<0.05), but differences no longer were significant after correcting for adiposity and circulating metabolic factors. Overall, values for the young controls differed with those for the sedentary, but not the exercising older men. Older men who exercise regularly do not demonstrate vascular endothelial oxidative stress, and this may be a key molecular mechanism underlying their reduced risk of cardiovascular diseases.

Effect of tissue mechanical properties on cuff-based blood pressure measurements.

This paper presents a 3D finite element upper arm model, validated by experiments as well as clinical data, used to study the error introduced in blood pressure measurements due to variability of arm tissue mechanical properties. The model consists of three separate cylindrical parts: soft tissue, bone and brachial artery. The artery volume changes under the cuff are used to represent the cuff pressure oscillations for analyzing blood pressure measurements. These oscillation trends are identical to observed clinical data. Also an upper arm simulator is designed and built for model validation. The model shows that the variation of soft tissue compressibility introduces an error up to 5% in blood pressure measurements. It is also revealed that the variation of the brachial artery and arm tissue stiffness has an insignificant effect on oscillometric blood pressure measurement method.

Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis.

While the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise trained for 16-20 wk (n = 8) and a group that remained sedentary (n = 8). We found that a total of 130 genes were upregulated and 84 genes downregulated in brachial artery endothelial cells with exercise training (>1.5-fold and false discovery rate <15%). In contrast, a total of 113 genes were upregulated and 31 genes downregulated in internal mammary artery endothelial cells using the same criteria. Although there was an overlap of 66 genes (59 upregulated and 7 downregulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature.

Long-term exercise training does not alter brachial and femoral artery vasomotor function and endothelial phenotype in healthy pigs.

Although the beneficial effects of exercise training on conduit artery endothelial function are well-established in animals and humans with compromised basal function, whether exercise exerts favorable effects on a healthy endothelium is inconclusive. We sought to determine whether long-term exercise training enhances endothelial function in peripheral conduit arteries of healthy pigs. Using a retrospective analysis of data collected in our laboratory (n = 127), we compared in vitro brachial and femoral artery endothelium-dependent and -independent relaxation between a group of pigs that exercise-trained for 16-20 wk and a group that remained sedentary. No differences in vasomotor function were found between the 2 groups (P > 0.05). Additionally, in a subset of pigs (n = 16), expression levels of 18 proteins that are typically associated with the atherosclerotic process were measured by immunoblot analysis of endothelial cell scrapes obtained from the brachial and femoral arteries. We found no differences (P > 0.05) in endothelial gene expression between these exercise-trained and sedentary healthy pigs. These results indicate that pigs exhibiting the classic training-induced adaptations do not demonstrate enhanced endothelium-dependent dilation nor reveal a more atheroprotected endothelial cell phenotype in their brachial and femoral arteries than their sedentary but otherwise healthy counterparts.

Endothelial function is impaired in HIV-infected patients with lipodystrophy.

BACKGROUND: Data supporting a link between body-fat distribution changes and cardiovascular disease risk in HIV-infected patients are scarce and contradictory. We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy. METHODS: HIV-infected patients with and without lipodystrophy were prospectively enrolled. Endothelial function was measured through flow-mediated dilatation (FMD) of the brachial artery. Plasma levels of several biomarkers of inflammation, endothelial activation and coagulation associated with adipose tissue and endothelial dysfunction were determined. RESULTS: The study included 110 patients, 55 of them with lipodystrophy. FMD was significantly lower in patients with lipodystrophy than in those without lipodystrophy (median [IQR] 3.1% [0.4-8.9] versus 6.3% [3.3-10.7]; P=0.004). Patients with isolated lipoatrophy exhibited the lowest FMD (2.6% [0-6.6]; P(Kruskal-Wallis)=0.02). Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6 (Spearman's rho =-0.26; P=0.007). In a multivariate regression model with the lowest quartile of FMD as the dependent variable and lipodystrophy, traditional cardiovascular risk factors, 10-year Framingham risk score, pro-atherosclerotic biomarkers and HIV-related variables as predictors, the only independent predictor of endothelial dysfunction was lipodystrophy (odds ratio 5.22, 95% confidence interval 1.76-15.46; P=0.003). CONCLUSIONS: Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.

Protein expression in vascular endothelial cells obtained from human peripheral arteries and veins.

Studying molecular mechanisms of vascular endothelial function in humans is difficult in part because of limited access to arteries. Access to peripheral veins is more practical. We determined if differences in protein expression of endothelial cells (EC) collected from a peripheral artery are reflected in measurements made on EC obtained from peripheral veins. EC were collected from the brachial artery and an antecubital vein of 106 healthy adults (60 men and 46 women, age 18-77 years). Quantitative immunofluorescence was used to measure protein expression of endothelial nitric oxide synthase (eNOS), Ser-1177 phosphorylated eNOS, manganese superoxide dismutase, nitrotyrosine, xanthine oxidase and nuclear factor-kappaB p65. Protein expression in EC obtained from brachial artery and antecubital vein sampling was moderately to strongly related (r = 0.59-0.81, all p < 0.0001, mean r = 0.70). Moreover, differences between subgroups in the lowest and highest tertiles of protein expression in EC obtained from arterial samples were consistently reflected in EC obtained from venous collections. These findings indicate that interindividual and group differences in expression of several proteins involved in nitric oxide production, oxidant production, antioxidant defense and inflammatory signaling in EC obtained from brachial artery sampling are consistently reflected in EC obtained from venous samples. Thus, EC collected from peripheral veins may provide a useful surrogate for EC obtained from arteries for measurements of EC protein expression in humans.

Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation.

PURPOSE: We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function. METHODS: Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy > or = 1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133/VEGFR-2 cells) and assayed in culture for EPC colony-forming units (CFUs). In 23 patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite was measured in blood as an indicator of intravascular nitric oxide. RESULTS: Endothelial progenitor cells increased from 35 +/- 5 to 63 +/- 10 cells/mL, and EPC-CFUs increased from 0.9 +/- 0.2 to 3.1 +/- 0.6 per well (both P < .01), but 11 patients had no increase in either measure. Those patients whose EPCs increased from baseline showed significant increases in nitrite and reduction in annexin-V staining (both P < .01) versus no change in patients without increase in EPCs. Over the course of the program, EPCs increased prior to increase in nitrite in the blood. CONCLUSIONS: Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood.

Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB.

Aging is associated with impaired vascular endothelial function, as indicated in part by reduced endothelium-dependent dilation (EDD). Decreased EDD with aging is thought to be related to vascular endothelial cell oxidative stress, but direct evidence is lacking. We studied 95 healthy men: 51 young (23+/-1 years) and 44 older (63+/-1 years). EDD (brachial artery flow-mediated dilation) was approximately 50% lower in older versus young men (3.9+/-0.3% versus 7.6+/-0.3%, P<0.01; n=42 older/n=51 young). Abundance of nitrotyrosine (quantitative immunofluorescence), an oxidatively modified amino acid and marker of oxidative stress, was higher in endothelial cells (ECs) obtained from the brachial artery (1.25+/-0.12 versus 0.61+/-0.11 nitrotyrosine intensity/human umbilical vein EC [HUVEC] intensity, P=0.01; n=11 older/n=11 young) and antecubital veins (0.55+/-0.04 versus 0.34+/-0.03, P<0.05; n=19 older/n=17 young) of older men. Flow-mediated dilation was inversely related to arterial EC nitrotyrosine expression (r=-0.62, P=0.01; n=22). In venous samples, EC expression of the oxidant enzyme NAD(P)H oxidase-p47(phox) was higher in older men (0.71+/-0.05 versus 0.57+/-0.05 NAD[P]H oxidase-p47(phox) intensity/HUVEC intensity, P<0.05; n=19 older/n=18 young), whereas xanthine oxidase and the antioxidant enzymes cytosolic and mitochondrial superoxide dismutase and catalase were not different between groups. Nuclear factor-kappaB p65, a component of the redox-sensitive nuclear transcription factor nuclear factor-kappaB, was elevated in both arterial (0.73+/-0.07 versus 0.53+/-0.05 NF-kappaB p65 intensity/HUVEC intensity, P<0.05; n=9 older/n=12 young) and venous (0.65+/-0.07 versus 0.34+/-0.05, P<0.01; n=13 older/n=15 young) EC samples of older men and correlated with nitrotyrosine expression (r=0.51, P<0.05 n=16). These results provide direct support for the hypothesis that endothelial oxidative stress develops with aging in healthy men and is related to reductions in EDD. Increased expression of NAD(P)H oxidase and nuclear factor-kappaB may contribute to endothelial oxidative stress with aging in humans.

Exercise-induced improvement in vasodilatory function accompanies increased insulin sensitivity in obesity and type 2 diabetes mellitus.

OBJECTIVE: The present study was undertaken to determine whether improved vasodilatory function accompanies increased insulin sensitivity in overweight, insulin-resistant subjects (OW) and type 2 diabetic patients (T2DM) who participated in an 8-wk exercise training regimen. DESIGN: Before and after training, subjects had euglycemic clamps to determine insulin sensitivity. Brachial artery catheterization was done on another occasion for measurement of vasodilatory function. A lean, healthy, untrained group was studied as nonexercised controls. RESULTS: Training increased oxygen consumption (VO2) peak [OW, 29 +/- 1 to 37 +/- 4 ml/kg fat-free mass (FFM).min; T2DM, 33 +/- 2 to 43 +/- 3 ml/kg FFM.min; P < 0.05] and improved insulin-stimulated glucose disposal (OW, 6.5 +/- 0.5 to 7.2 +/- 0.4 mg/kg FFM.min; T2DM, 3.8 +/- 0.3 to 4.2 +/- 0.3 mg/kg FFM.min; P < 0.05) in insulin resistance. OW and T2DM, before training, had decreased acetylcholine chloride (ACh)- and sodium nitroprusside-mediated vasodilation and decreased reactive hyperemia compared with lean controls. Training increased the vasodilatory response to ACh [OW (30 microg ACh/min), 12.2 +/- 3.4 to 19 +/- 4.2 ml/100 g.min; T2DM (30 microg ACh/min), 10.1 +/- 1.5 to 14.2 +/- 2.1 ml/100 g.min; P < 0.05] in both groups without affecting nitroprusside response. CONCLUSION: Because vasodilatory dysfunction has been postulated to contribute to insulin resistance, the exercise-induced improvement in vasodilatory function may signify changes in the endothelium that could contribute to the improvement in insulin sensitivity observed after aerobic exercise training.

Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout.

Hydrogen sulfide (H(2)S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H(2)S from NaHS and examined the effects on isolated efferent branchial arteries from steelhead (stEBA) or rainbow (rtEBA) trout. H(2)S concentration was measured colorimetrically (CM) and with ion-selective electrodes (ISE) in rainbow trout plasma. NaHS produced a triphasic response consisting of a relaxation (phase 1), constriction (phase 2), and relaxation (phase 3) in both unstimulated vessels and in stEBA precontracted with carbachol (Carb). Phase 1 and phase 3 in stEBA were decreased and phase 2 increased in unstimulated vessels by K(+)(ATP) channel inhibition (glibenclamide), or a cocktail of inhibitors of cyclooxygenase, lipoxygenase, and cytochrome P-450 (indomethacin, esculetin, and clotrimazole). Inhibition of soluble guanylate cyclase with ODQ o NS-2028 inhibited phase 3 in stEBA, although NaHS decreased cGMP production by tEBA. stEBA phase 2 contractions were partially inhibited by the myosin light chain kinase inhibitor, ML-9, but unaffected by L-type calcium channel inhibition (methoxyverapamil), whereas contraction in tEBA was partially inhibited by nifedipine or removal of extracellular calcium. Phase 3 relaxations were more pronounced in stEBA precontracted with Carb and no epinephrine (NE) than those cont acted by KCl or K(2)SO(4). stEBA phase 2 and phase 3 responses were dose dependent (EC(50) = 1.1 +/- 1.2 x 10(-3) M and 6.7 +/- 0.9 x 10(-5) M, respectively; n = 7). NaHS was also vasoactive in steelhead bulbus arteriosus, celiac mesenteric arteries, and anterior cardinal veins. Rainbow trout plasma sulfide concentration was 4.0 +/- 0.3 x 10(-5) M, n = 4 (CM) and 3.8 +/- 0.4 x 10(-5) M, n = 9 (ISE); similar to phase 3 EC(50). Because NaHS has substantial vasoactive effects at physiological plasma concentrations, we propose that its soluble derivative, H(2)S, is a tonically active endogenous vasoregulator in trout.

Different effect of antihypertensive drugs on conduit artery endothelial function.

To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, n=28), amlodipine (5 to 10 mg, n=28), atenolol (50 to 100 mg, n=29), nebivolol (5 to 10 mg, n=28), telmisartan (80 to 160 mg, n=29), and perindopril (2 to 4 mg, n=28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 microg/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (P<0.01) lower flow-mediated dilation (5.2+/-1.9%) as compared with healthy control subjects (7.1+/-2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1+/-2 to 6.4+/-2.4%; P<0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.

Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C.

BACKGROUND: Previous studies in patients with a history of Kawasaki disease have focused on vascular endothelial function in coronary arteries, and the endothelial function of systemic arteries is not fully understood. Furthermore the effect of vitamin C on systemic endothelial function after Kawasaki disease has not been elucidated. OBJECTIVES: We attempted to analyze endothelium-dependent vasodilatation in the brachial artery after Kawasaki disease by using high resolution ultrasonography and to investigate whether the acute administration of vitamin C could restore such systemic endothelial dysfunction. METHODS: We compared 39 patients (7.1 +/- 2.7 years) 1.0 to 9.6 years after acute Kawasaki disease with 17 matched healthy subjects (7.0 +/- 3.1 years) as controls. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilatation) and sublingual nitroglycerin (causing endothelium-independent dilatation). RESULTS: The percent change in diameter of the brachial artery induced by reactive hyperemia in the patients with a history of Kawasaki disease (6.2 +/- 3.9%) was significantly lower than that in the control group (14.1 +/- 6.8%; P < 0.0001). No significant difference could be found in percent change in diameter induced by sublingual administration of nitroglycerin between the control (33.2 +/- 13.7%) and the patients with a history of Kawasaki disease (30.6 +/- 9.2%; P = 0.49). There was no significant difference in percent change in diameter of the brachial artery induced by reactive hyperemia between the patients who received gamma-globulin (6.0 +/- 4.0%) and those who did not receive gamma-globulin (7.9 +/- 3.3%; P = 0.33). Intravenous infusion of vitamin C significantly increased the percent change in diameter of brachial artery induced by reactive hyperemia in 19 patients with history of Kawasaki disease (6.6 +/- 3.5 to 13.0 +/- 5.5%; P < 0.0001), whereas no significant increase was seen in the percent change in diameter of brachial artery induced by reactive hyperemia in 20 patients with history of Kawasaki disease after placebo administration (6.5 +/- 4.5 to 7.3 +/- 4.9%; P = 0.20). CONCLUSIONS: Our study showed decreased percent change in diameter of the brachial artery induced by reactive hyperemia in patients with history of Kawasaki disease compared with the healthy children, indicating that systemic endothelial dysfunction exits after Kawasaki disease. Although such systemic endothelial dysfunction after Kawasaki disease is not influenced by early treatment with high dose gamma-globulin in the acute stage of Kawasaki disease, it can be restored by the acute intravenous administration of vitamin C.

Arterial stiffness and endothelial function in patients with beta-thalassemia major.

BACKGROUND: Increased iron store has been linked to risk of cardiovascular disease. Structural alterations of arteries in beta-thalassemia major patients and in vitro functional disturbance of vascular endothelial cells by thalassemic serum have been described. We sought to determine whether arterial stiffness and endothelial function are altered in vivo. METHODS AND RESULTS: Thirty thalassemia patients (16 male) aged 22.2+/-7.4 years were recruited. Left ventricular (LV) mass and function were assessed echocardiographically. Carotid and brachioradial artery stiffness was assessed by stiffness index and pulse-wave velocity (PWV), respectively. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation [FMD]) and sublingual glyceryl trinitrate. These indexes were compared with those of 30 age- and sex-matched controls. None of the patients had LV systolic or diastolic dysfunction. When compared with controls, patients had greater absolute (113.8+/-38.0 versus 109.0+/- 32.6 g, P=0.04) and indexed (82.4+/-17.5 versus 66.7+/-12.7 g/m(2), P<0.001) LV mass, carotid artery stiffness index (8.1+/-3.5 versus 5.5+/-1.6, P<0.001), and brachioradial PWV (8.9+/-2.4 versus 7.9+/-1.7 m/s, P= 0.03). Their FMD was impaired (3.5+/-3.3% versus 8.8+/-3.9%, P<0.001), whereas glyceryl trinitrate- mediated dilation was preserved (17.9+/-7.6% versus 16.3+/-6.1%, P=0.40). Both stiffness index and PWV correlated inversely with magnitude of FMD (r=-0.40, P=0.03; r=-0.41, P=0.03) and positively with indexed LV mass (r=0.50, P=0.005; r=0.40, P=0.027). Nonetheless, no significant correlation existed between ferritin level and carotid stiffness, PWV, or FMD. CONCLUSIONS: Increased arterial stiffness, endothelial dysfunction, and LV hypertrophy occur in patients with beta-thalassemia major, which may result in reduction of mechanical efficiency of the heart.

Noninvasive study of endothelial function in white coat hypertension.

Several studies have demonstrated that endothelial dysfunction is present in patients with essential hypertension. However, the presence of endothelial dysfunction in patients with white coat hypertension has not been studied. We evaluated the variation in the diameter of the brachial artery produced by flow-mediated dilation after a mechanical stimulus in patients with recently diagnosed mild to moderate sustained essential hypertension compared with patients with white coat hypertension. A total of 29 patients fulfilled inclusion criteria; 15 healthy volunteers were also included. After 24-hour ambulatory blood pressure monitoring, 15 patients were classified with sustained essential hypertension; 14 patients with white coat hypertension. Vascular ultrasound scans were performed according to the method described by Celermajer et al, with modification for noninvasive determination of endothelial dysfunction. Basal brachial artery diameter did not differ significantly among the 3 groups. Changes in arterial diameter 60 seconds after cuff deflation were higher in the control group compared with both hypertensive groups, but no significant differences were found between the sustained essential hypertension group and the white coat hypertension group. Flow-mediated dilation was similar in white coat hypertensives and sustained essential hypertensives. The presence of endothelial dysfunction in subjects with white coat hypertension suggests that it should not be considered a harmless trait and that white coat hypertension has common features with sustained essential hypertension.

[A non-invasive method for detecting endothelium-dependent dilation].

Using high resolution ultrasound, we measured the diameter of brachial arteries at rest, during reactive hyperemia and after glyceryl trinitrate (GTN) taking in 22 healthy persons. The results showed that brachial artery dilation was present both in reactive hyperemia and response to GTN. The mean flow-mediated dilation was 13.8 +/- 3.9% increment. The mean increment of dilation in response to GTN was 24.9 +/- 9.7%. The diameters of brachial arteries during reactive hyperemia and after sublingual GTN had significant difference compared with that in baseline (P < 0.01). It indicates that increased flow may mediate endothelium-dependent vessel dilatation and GTN cause endothelium-independent vessel dilatation in normal subjects. This paper presents a new non-invasive method of detecting endothelium-dependent dilation, which is proved to be simple, secure and practical.

Sumatriptan-induced saphenous venoconstriction in the anaesthetized dog through 5-HT1-like receptor activation.

1. The role of vasoconstrictor 5-HT1-like receptors in the control of vascular reactivity in vivo has been relatively little studied, particularly with regards to venous function. Using an anaesthetized dog model, we have investigated the haemodynamic profile of the selective 5-HT1-like agonist, sumatriptan, focussing on the reactivity of the saphenous venous bed. The key feature of our experimental model was the implantation of ultrasonic crystals on the adventitial surface of the lateral saphenous vein to provide direct and continuous measurement of drug-induced changes in vein diameter. Saphenous vein pressure was measured simultaneously via a proximal branch. 2. Sumatriptan 1-30 micrograms kg-1, i.v., produced pronounced dose-related reductions in saphenous vein diameter which reached congruent to 40% at the highest dose tested. Sumatriptan also produced modest increases in mean blood pressure, total peripheral resistance and left ventricular end diastolic pressure but had little or no effect on cardiac output, heart rate, cardiac contractility or saphenous venous pressure. Sumatriptan-induced reductions in saphenous vein diameter were strongly antagonized by the 5-HT1-receptor antagonist, methiothepin (0.3 mg kg-1, i.v.) but were unaffected by the 5-HT2 antagonist, ketanserin (0.3 mg kg-1, i.v.). 3. Hence, 5-HT1-like receptor stimulation in vivo can result in a powerful local venoconstrictor effect.

The special status of the pulmonary arch artery in the branchial arch system of the rat.

A renewed study of the development of the branchial arch system was essential in view of the special morphologic characteristics of the ductus arteriosus, which derives from the pulmonary arch artery or sixth branchial arch artery. In congenital heart disease certain aorto-pulmonary collateral arteries have a marked histological similarity to the ductus arteriosus. To gain a better insight into the development of these vessels, 27 rat embryos, with the number of somites ranging between 19 and 41, were studied. Most embryos were collected after shortterm in vitro-culture, allowing precise staging of age and development. The vascular system of these embryos was injected with Indian ink, to enable easy recognition of even the smallest endothelium-lined vessels. The embryos were serially sectioned (3-5 microns) and reconstructed using a graphic method. The results show that the pulmonary arch artery differs from the other arch arteries in that it is the most cranial vessel of a system of ventral splanchnic arteries, which connects the pulmonary plexus with the dorsal aortae at an early stage. With the exception of the pulmonary arch artery, these connections are transient. The pulmonary arteries develop from the remaining parts of the plexus. It is argued that these connections can persist in the human as aorto-pulmonary collaterals, in certain cases with abnormalities in the pulmonary part of the cardiac outflow tract.