Effect of green tea consumption on endothelial function and circulating endothelial progenitor cells in chronic smokers.

BACKGROUND: The present study was designed to investigate the effect and relationship of endothelial function and endothelial progenitor cells (EPCs) by green tea consumption in chronic smokers. The numbers of circulating EPCs have an inverse correlation with chronic smoking and endothelial dysfunction. Green tea catechin improved endothelial dysfunction in chronic smokers. METHOD AND RESULTS: In 20 young healthy smokers, endothelial functions, defined by flow-mediated endothelium dependent vasodilation (FMD) of the brachial artery via ultrasound as well as the number of EPCs isolated from peripheral blood, were determined at baseline and at 2 weeks after green tea consumption (8 g/day). Circulating EPCs were quantified by flow cytometry as CD45lowCD34+KDR2+ cells and by acyl-low-density lipoprotein and fluorescein isotiocyanate-lectin double positive cells after culture for 7 days. Clinical characteristics and laboratory findings were not significantly different between the baseline and at 2 weeks after green tea intake. EPC levels were inversely correlated with the number of cigarettes smoked. Circulating EPCs by flow cytometry (78.6+/-72.6 vs 156.1+/-135.8 /ml, p<0.001) and cultured EPCs (118.2+/-35.7 vs 169.31+/-58.3/10 field, p<0.001) increased rapidly at 2 weeks after green tea consumption. FMD was significantly improved after 2 weeks (7.2+/-2.8 vs 9.3+/-2.4, p<0.001). The FMD correlated with EPC counts (r=0.67, p=0.003) before treatment and after 2 weeks (r=0.60, p=0.013). CONCLUSIONS: A short-term administration of green tea consumption induces a rapid improvement of EPC levels and FMD. Green tea consumption may be effective to prevent future cardiovascular events in chronic smokers.     

The effect of acute hyperinsulinemia on arterial pressure in healthy individuals

To assess if induced hyperinsulinemia enhances blood pressure (BP), three tests were performed to nine healthy volunteers as follows: A. After an oral dextrose load (75 g), 250 ml of 0.9% NaCl plus 25 g dextrose were infused in three hours. B. The same procedure, plus 15 U of regular insulin in the intravenous solution. C. (control) The same procedure but without insulin and dextrose. Pulse and BP were measured every 15 minutes, serum glucose and insulin were determined hourly. Hyperinsulinemia from 2 to 7-fold the basal value was induced in the test A, and from 7 to 30-fold in the test B (P less than 0.01). BP did not rise with hyperinsulinemia, but a slight and nonsignificant decrease of mean BP and higher heart rate (P less than 0.05) were noticed at the third hour in the test B. Acute hyperinsulinemia do not cause high BP. A cause-effect relationship between hyperinsulinemia and hypertension is still unproved.     

Inhibitory effect of Chinese green tea on endothelial cell-induced LDL oxidation

Green tea has been shown to inhibit Cu(2+)-induced LDL oxidation and suppress lipoxygenase activity. Since LDL oxidation is a characteristic feature of atherogenesis and lipoxygenase is involved in the disease process, the effect of Lung Chen Tea, a non-fermented Chinese green tea, on LDL oxidation induced by human umbilical cord vascular endothelial cell was investigated in the present study. Lung Chen Tea was extracted with methanol and the dried powder was redissolved in water before extraction with chloroform and then ethyl acetate. Lung Chen Tea, chloroform and ethyl acetate fractions dose-dependently reduced LDL oxidation and decreased its relative electrophoretic mobility (P<0.001) when compared to the oxidized LDL. The lipid peroxidation products, thiobarbituric acid reactive substances, and cellular cholesterol were also significantly lowered by 5 and 10 microg/ml Lung Chen Tea (P<0.001) in a dose-dependent manner. The remaining aqueous layer, which was devoid of catechins after chloroform and ethyl acetate extractions, did not prevent LDL oxidation. The results of this study demonstrated that Lung Chen Tea and catechin-rich fractions significantly prevented endothelial cell induced LDL oxidation. The consumption of Lung Chen Tea may therefore lower the risk of coronary heart diseases.     

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.     

The effect of acute hypoxia on right ventricular function in healthy adults

Right ventricular ejection fraction and right ventricular volumes were derived in 12 healthy male subjects using krypton-81m equilibrium radionuclide ventriculography whilst subjects breathed 30% (high inspired oxygen) and then 8-12% oxygen in nitrogen mixture (hypoxia). 'Physiological' tricuspid valve regurgitation was identified in 7 of the subjects by Doppler echocardiography, and right ventricular peak systolic pressure was estimated during high inspired oxygen and during hypoxia. Mean right ventricular peak systolic pressure was 24.1 +/- 3.3 mmHg during high inspired oxygen and increased to 41.3 +/- 8.4 mmHg during hypoxia (P less than 0.01). Mean right ventricular ejection fraction was 0.612 +/- 0.075 during high inspired oxygen and was unchanged at 0.590 +/- 0.073 during hypoxia. There was no significant change in right ventricular end-diastolic volume or stroke volume in response to hypoxia. The systolic performance of the normal right ventricle is well-maintained during an acute rise in afterload induced by hypoxia.     

Oral L-arginine improves endothelial function in healthy individuals older than 70 years

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 +/- 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 +/- 0.18 mm. L-Arginine significantly improved FMD (to 5.7 +/- 1.2%, p < 0.0001), whereas placebo had no effect (-0.25 +/- 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased significantly (114.9 +/- 11.6 versus 57.4 +/- 5.0 micromol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 +/- 0.2 versus 1.0 +/- 0.1 micromol/l; p < 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p < 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.     

The protective effect of habitual tea consumption on hypertension

BACKGROUND: Tea has long been believed to possess hypotensive effects in popular Chinese medicine. However, conflicting results have been shown among human trials and animal studies on the relation between tea consumption and blood pressure. Epidemiological evidence about the long-term effect of tea on hypertensive risk is also inconsistent. METHODS: We examined the effect of tea drinking, measured in detail for the past decades, on the risk of newly diagnosed hypertension in 1507 subjects (711 men and 796 women), 20 years or older, who did not have a hypertensive history during 1996 in Taiwan. RESULTS: Six hundred subjects (39.8%) were habitual tea drinkers, defined by tea consumption of 120 mL/d or more for at least 1 year. Compared with nonhabitual tea drinkers, the risk of developing hypertension decreased by 46% for those who drank 120 to 599 mL/d and was further reduced by 65% for those who drank 600 mL/d or more after carefully adjusting for age, sex, socioeconomic status, family history of hypertension, body mass index, waist-hip ratio, lifestyle factors (total physical activity, high sodium intake, cigarette smoking, alcohol consumption, and coffee drinking), and dietary factors (vegetable, fruit, unrefined grain, fish, milk, visible-fat food, and deep fried food intake). However, tea consumption for more than 1 year was not associated with a further reduction of hypertension risk. CONCLUSION: Habitual moderate strength green or oolong tea consumption, 120 mL/d or more for 1 year, significantly reduces the risk of developing hypertension in the Chinese population.     

Influence of acute and chronic mineralocorticoid excess on endothelial function in healthy men

Aldosterone has rapid nongenomic effects in the human vasculature. However, data are not uniform and little is known about chronic effects of aldosterone. Therefore, we investigated acute and chronic effects of elevated aldosterone levels on endothelial function in the forearm vasculature of healthy men. In a first crossover study, the effects of arterial aldosterone infusion in ascending doses (3.3 to 55 pmol/min per 1000 mL forearm volume) on forearm blood flow were investigated in 8 healthy men (26+/-2 years). In a second study, endothelium-dependent (acetylcholine; 0.08, 0.275, and 2.75 micromol/min per 1000 mL) and endothelium-independent (sodium nitroprusside 0.02 micromol/min per 1000 mL) vasodilation and basal nitric oxide formation (forearm blood flow response to blockade by N(G)-monomethyl-l-arginine 8 micromol/min per 1000 mL) were tested in 10 healthy men (age 30+/-5 years) at baseline, during infusion of 55 pmol/1000 mL per min aldosterone (acute effects), and after 0.3 mg/d oral fludrocortisone for 2 weeks (chronic effects) on separate days. Forearm blood flow was assessed by venous occlusion plethysmography. No change in forearm blood flow was seen with aldosterone infusion alone. Acute coinfusion of aldosterone increased vasodilation to sodium nitroprusside by 93% (P<0.01) and to acetylcholine by 60% (P=0.14). Response to N(G)-monomethyl-l-arginine did not change. After 2 weeks of oral fludrocortisone, response to acetylcholine was enhanced by 72% compared with baseline (P=0.03). Additionally, response to N(G)-monomethyl-l-arginine was enhanced by 80% compared with baseline (P=0.05). Aldosterone acutely enhances vasodilation to exogenous nitric oxide whereas mineralocorticoid excess for 2 weeks enhances basal nitric oxide bioactivity and improves endothelium dependent, nitric oxide-mediated vasodilation in the forearm vasculature of healthy men.     

Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals

OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.     

Cardioprotective effect of a biofermented nutraceutical on endothelial function in healthy middle-aged subjects

We tested a biofermented nutraceutical (FPP) that has been previously shown to positively modulate nitric oxide (NO). Forty-two healthy middle-aged subjects were given 3 grams of FPP three times a day for 6 weeks, and tests were repeated at 3 and 6 weeks; the control group was given a placebo. Flow-mediated dilation (FMD) was measured together with NO compounds (nitrogen oxides [NOx]: NO(2)(-)+NO(3)(-)) plasma levels and asymmetrical dimethylarginine (ADMA). In the interventional group, overall FMD significantly increased from 4.2% to 7.3% (p<0.05 vs. placebo). A significant increase in plasma NO and a decrease in ADMA were detected after consumption of FPP (p<0.01). Although larger studies are awaited, it appears that, at least in healthy individuals, such nutraceutical intervention by positively acting on significant cardiovascular parameters can be considered in the armamentarium of a proactive age-management strategy.     

The effect of diet on endothelial function

Endothelial dysfunction is an early precursor to atherosclerosis. Lifestyle interventions, including diet, have been shown to affect endothelial function. High-fat diets have been shown to impair endothelial function, and diets such as the Mediterranean diet have been associated with improved endothelial function. This review discusses the effects of diet, dietary supplements such as folic acid, polyphenols, and antioxidant vitamins on endothelial function. We provide a summary of the current data linking diet with endothelial function and explore controversies within this field.     

The effect of loperamide on anorectal function in normal healthy men.

Loperamide improves anorectal functioning in patients with diarrhea and incontinence. Loperamide reduces sensitivity of the recto-anal inhibitory reflex and increases internal anal sphincter tone. Additionally, it has an effect on rectal compliance in incontinent patients with diarrhea. We studied the effect of loperamide versus placebo at different distances from the anal verge in 18 healthy male volunteers, using standard anorectal manometry was a double-blind, two-factorial design. We found that the recto-anal inhibitory reflex is most pronounced when stimulated in regions close to the anal canal and that distention stimuli are also perceived best in that region. Both effects are counteracted by loperamide. We found no effect on internal sphincter tone or rectal compliance. These results imply a gradient of sensitivity for rectal perception and the recto-anal inhibitory reflex in healthy volunteers. Loperamide action on both mechanisms suggests a common mediator for both effects.     

Pregnancy-related hyperlipidemia and endothelial function in healthy women.

BACKGROUND: The purpose of the present study was to investigate pregnancy-related changes in the maternal serum lipid profile and endothelial function. METHODS AND RESULTS: As part of the population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland, 57 pregnant Finnish women and 62 control women matched for age and smoking were examined throughout gestation. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined and concomitantly endothelium-dependent brachial artery flow mediated dilation (FMD) was measured by ultrasound. During pregnancy serum TC, LDL-C, HDL-C, TG and very-low-density lipoprotein cholesterol increased significantly when compared with the non-pregnant state (p<0.001 for each) and towards the end of pregnancy (p<0.001, p<0.001, p=0.007, p<0.001, p<0.001). FMD increased towards the end of pregnancy and there was a statistically significant direct correlation between gestational age and FMD% (r=0.345, p=0.010). Brachial artery diameter at rest and FMD% were negatively correlated in pregnant (r=-0.280, p=0.035) and non-pregnant women (r=-0.360, p<0.004). The univariate correlation analysis showed a direct correlation between maternal serum TC (r=0.333, p=0.012) and TG (r=0.366, p=0.006) and FMD%, whereas a negative non-significant correlation was found in non-pregnant women. In a multivariate model, vessel size (beta=-0.436, p=0.001) and TG (beta=0.502, p<0.001) were the most powerful predictors for FMD% in pregnancy, the influence of other lipids was non-significant. CONCLUSIONS: In healthy pregnant women increased gestational age is associated with improved endothelium-dependent vasodilation responses regardless of concurrently appearing lipid changes.     

The acute effect of aerobic exercise on brachial artery endothelial function in renal transplant recipients

This study compared the effect of a 30-minute walk on brachial artery endothelial vasodilatation in kidney transplant (KT) recipients and healthy controls (HCs). Endothelial-dependent vasodilatation was measured by ultrasound before and after exercise. The HCs experienced a significant increase in vasodilatation after exercise 1 minute postocclusion when compared with the KT recipients (22%+/-13% vs 3%+/-4%; P<.05). Also, the HCs had a significantly higher vasodilatation from pre-treadmill walk to post-treadmill walk (1 minute postocclusion) when compared with KT recipients (from 3%+/-6% to 22%+/-13% vs 1%+/-3% to 3%+/-4%; P<.05). This acute vasodilatory response observed in the HCs may be related to the immediate release of nitric oxide and the combined response to shear stress and exercise. The KT recipients had several coronary artery disease risk factors that may have adversely affected endothelial function.     

Effect of dark chocolate on arterial function in healthy individuals

BACKGROUND: Epidemiologic studies suggest that high flavonoid intake confers a benefit on cardiovascular outcome. Endothelial function, arterial stiffness, and wave reflections are important determinants of cardiovascular performance and are predictors of cardiovascular risk. METHODS: The effect of flavonoid-rich dark chocolate (100 g) on endothelial function, aortic stiffness, wave reflections, and oxidant status were studied for 3 h in 17 young healthy volunteers according to a randomized, single-blind, sham procedure-controlled, cross-over protocol. Flow-mediated dilation (FMD) of the brachial artery, aortic augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV) were used as measures of endothelial function, wave reflections, and aortic stiffness, respectively. Plasma oxidant status was evaluated with measurement of plasma malondialdehyde (MDA) and total antioxidant capacity (TAC). RESULTS: Chocolate led to a significant increase in resting and hyperemic brachial artery diameter throughout the study (maximum increase by 0.15 mm and 0.18 mm, respectively, P < .001 for both). The FMD increased significantly at 60 min (absolute increase 1.43%, P < .05). The AIx was significantly decreased with chocolate throughout the study (maximum absolute decrease 7.8%, P < .001), indicating a decrease in wave reflections, whereas PWV did not change to a significant extent. Plasma MDA and TAC did not change after chocolate, indicating no alterations in plasma oxidant status. CONCLUSIONS: Our study shows for the first time that consumption of dark chocolate acutely decreases wave reflections, that it does not affect aortic stiffness, and that it may exert a beneficial effect on endothelial function in healthy adults. Chocolate consumption may exert a protective effect on the cardiovascular system; further studies are warranted to assess any long-term effects.     

Effect of alcohol on endothelial function in healthy subjects

While studies have shown that red wine improves endothelial function, the effect of pure alcohol, the common denominator of all alcoholic beverages, on endothelial function has not been defined. The effect of oral intake of alcohol (one ounce--a dose corresponding to two drink equivalents) on flow-mediated dilatation of the brachial artery was studied in 12 healthy subjects using high-resolution ultrasonography according to a randomized, sham procedure-controlled, single-blind protocol. Alcohol produced a significant vasodilatation of the brachial artery at resting conditions. Furthermore, it led to a significant increase of the brachial artery diameter at reactive hyperemia; however, the percentage flow-mediated dilatation did not change. This study shows, for the first time, that acute moderate intake of alcohol has a potent dilating effect on large arteries both at resting and at reactive hyperemic conditions, without affecting flow-mediated dilatation as a percentage. This may be useful for explaining the divergent effect of different alcoholic beverages on endothelial function and provides valuable insight into the mechanisms involved in the vascular effects of alcohol.     

Daily consumption of green tea catechin delays memory regression in aged mice

Almost all elderly people show brain atrophy and cognitive dysfunction, even if they are saved from illness, such as cardiac disease, malignancy and diabetes. Prevention or delay of brain senescence would therefore enhance the quality of life for older persons. Because oxidative stress has been implicated in brain senescence, we investigated the effects of green tea catechin (GT-catechin), a potential antioxidant, in senescence-accelerated (SAMP10) mice. The mouse is a model of brain senescence with short life span, cerebral atrophy and cognitive dysfunction. Mice were fed water containing 0.02% GT-catechin from 1- to 15-month-old. The mean dose was about 35 mg/kg/day. We found that daily consumption of GT-catechin prevented memory regression and DNA oxidative damage in these mice. GT-catechin did not prolong the lifetime of SAMP10 mice, but it did delay brain senescence. These findings suggest that continued intake of GT-catechin might promote healthy ageing of the brain in older persons.