Peak Forearm Blood Flow Research Articles

Vascular Endothelial Function Is Related to White Blood Cell Count and Myeloperoxidase Among Healthy Middle-Aged and Older Adults

Endothelium-dependent dilation (EDD) is impaired with aging, but there is significant variability among healthy middle-aged and older adults. We tested the hypothesis that EDD is related to white blood cell (WBC) count in healthy men and women aged 55 to 75 years (n=48) who have a WBC count within the clinically normal range. The peak forearm blood flow response to intrabrachial artery infusion of acetylcholine was inversely related to WBC count (r=-0.38; P=0.004) and was 34% smaller in subjects with higher versus lower WBC count (more versus less than the median of 5.0x10(9) cells per liter; P=0.001). Vascular smooth muscle responsiveness to NO (peak forearm blood flow response to sodium nitroprusside) was inversely related to WBC count (r=-0.30; P=0.02) but did not fully explain the associations with EDD. Inhibition of NO with N(G)-monomethyl-L-arginine reduced EDD in subjects with lower (-56%; P=0.01) but not higher WBC count. Tetrahydrobiopterin selectively improved EDD in subjects with higher WBC count (+35%; P=0.01) by increasing NO bioavailability. EDD was related (P<0.05) to neutrophil, eosinophil, and monocyte but not lymphocyte or basophil counts. Myeloperoxidase, which is secreted by neutrophils and monocytes, consumes NO and produces molecules that oxidize tetrahydrobiopterin, was inversely related to EDD (r=-0.35; P=0.02), and was 42% higher in subjects with a higher WBC count (P=0.02). No other factors contributed to the relation between EDD and WBC count. Among healthy middle-aged and older adults, impaired EDD is related to higher neutrophil, eosinophil, and monocyte-based WBC count mediated by reduced responsiveness to NO and increased myeloperoxidase-associated reductions in tetrahydrobiopterin and NO bioavailability.

Central, peripheral and resistance arterial reactivity: fluctuates during the phases of the menstrual cycle

The purpose of this study was to document the temporal changes in vascular reactivity occurring simultaneously in central, peripheral and microvascular resistance arteries in the same cohort of women during the normal menstrual cycle. Twenty-three (n = 23) women (mean age (+/-SD) = 19 +/- 1 y) were tested during four phases of a normal menstrual cycle. Delineation of the four phases occurred as follows: (1) the early follicular phase; (2) the late follicular (LF) phase; (3) the early luteal (EL) phase; and (4) the late luteal phase. Non-invasive measurement of central hemodynamics and peripheral artery pulse wave velocity (PWV) were performed using applanation tonometry. Measurement of peripheral endothelial function was determined by flow-mediated dilation (FMD) testing in the brachial artery and venous occlusion plethysmography in the forearm and calf resistance arteries. Additionally, plasma NOx and 17beta-estradiol (E) concentrations were measured. Both central (aortic) and peripheral blood pressure (BP) were lowest (P < 0.05) during the LF phase and BP reduction was sustained (P < 0.05) into the EL phase. The timing and amplitude of the reflected pressure wave were attenuated only during the LF phase (P < 0.05). No temporal changes were observed in either central (carotid-femoral) or peripheral PWV (femoral-dorsalis pedis, carotid-radial). Peak forearm and calf blood flow during reactive hyperemia were greatest in LF. Brachial FMD was greatest during the LF phase (P < 0.05). Plasma E and NOx concentrations were highest during the LF phase (P < 0.05). Young premenopausal women experienced an overwhelming pattern of reduced BP and increased systemic vascular reactivity during the LF phase prior to ovulation.

Plasma nitrate/nitrite levels are unchanged after long-term aerobic exercise training in older adults

Reduced nitric oxide (NO) production and bioactivity is a major contributor to endothelial dysfunction. Animal data suggest that improvements in endothelial function in response to aerobic exercise training may depend on the duration of the training program. However, no studies have examined changes in NO (as assessed by the major NO metabolites, nitrate and nitrite, NO x ) after long-term training in humans. In addition, aging may impair the ability of the vasculature to increase NO with exercise. Thus, we determined whether 24 weeks of aerobic exercise training increases plasma NO x levels in sedentary older adults. We also examined changes in forearm blood flow (FBF) at rest and during reactive hyperemia as a measure of vasomotor function. Plasma NO x levels were measured in 82 men and women using a modified Griess assay. FBF was assessed in a subset of individuals ( n = 15) using venous occlusion plethysmography. After 24 weeks of exercise training, there were significant improvements in maximum oxygen consumption, HDL cholesterol, triglycerides, and body fat. Changes in plasma NO x levels ranged from −14.83 to +16.69 μmol/L; however, the mean change overall was not significant (−0.33 ± 6.30 μmol/L, p = 0.64). Changes in plasma NO x levels were not associated with age, gender, race, HDL cholesterol, triglycerides, body weight, body fat, or maximal oxygen consumption. There were also no significant changes in basal FBF, peak FBF, hyperemic response, total hyperemic flow, or minimum forearm vascular resistance with exercise training. In conclusion, improvements in plasma NO x levels and FBF are not evident after long-term training in older adults.

Vascular and baroreceptor abnormalities in young males with a family history of hypertension

Vascular and baroreceptor abnormalities in 44 young males, mean age 21 years, comprising of offspring with (FH(+); n = 22) and without (FH(-); n = 22) hypertensive parents, were investigated. Peak forearm blood flow (FBF), which was defined as the highest blood flow obtained following reactive hyperaemia, was assessed using strain gauge plethysmography following 5 min of ischemia. Cardiopulmonary baroreceptor sensitivity was assessed using lower body negative pressure for 5 min at -20 mmHg and was determined by calculating change of stroke volume and forearm vascular resistance (FVR) to lower body negative pressure. Carotid baroreceptor sensitivity was assessed using neck suction at -20, -40, -60, and -80 mmHg and was calculated by dividing RR interval by systolic blood pressure. Augmentation index, a measure of wave reflection, was assessed using applanation tonometry and was calculated as the ratio of augmented pressure and pulse pressure. Peak FBF of FH(+) was 19% lower than the FH(-) (p = 0.02). Also FH(+) had 17% higher peak FVR compared to FH(-) (p = 0.04). However, there were no significant differences between groups for cardiopulmonary, carotid baroreceptor sensitivity, and augmentation index. These results suggest that peripheral vascular dysfunction appears earlier than abnormal baroreceptor sensitivity in young males with a family history of hypertension.

Vascular function is impaired early after the initiation of chronic cigarette smoking

Background The aim of this study was to assess resistance artery function in short-term chronic cigarette smokers and non-smoking control subjects. Methods Reactive hyperemia was assessed in 19 cigarette smokers (age 23 ± 1 years) and 19 non-smokers (age 23 ± 1 years). Results Cigarette smokers demonstrated a 23% lower peak forearm blood flow response compared with non-smokers (15.81 ± 0.66 vs. 20.58 ± 1.26 mL/min/100 mL, p < 0.05) and a 22% lower area under the curve of the reactive hyperemia response (607 ± 51.57 vs. 775 ± 53.51 mL/min/100 mL × 3 min, p < 0.05). Conclusions These results indicate that smoking-induced impairments of vascular function occur early after the initiation of chronic cigarette smoking.

Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase

To determine whether impaired endothelium-dependent dilation (EDD) in older adults is associated with changes in the expression of major vasoconstrictor or vasodilator proteins in the vascular endothelium, endothelial cells (EC) were obtained from the brachial artery and peripheral veins of 56 healthy men, aged 18-78 yr. Brachial artery EC endothelin-1 (ET-1) [0.99 +/- 0.10 vs. 0.57 +/- 0.10 ET-1/human umbilical vein EC (HUVEC) intensity, P = 0.01] and serine 1177 phosphorylated endothelial nitric oxide synthase (PeNOS) (0.77 +/- 0.09 vs. 0.44 +/- 0.07 PeNOS/HUVEC intensity, P < 0.05) (quantitative immunofluorescence) were greater, and EDD (peak forearm blood flow to intrabrachial acetylcholine) was lower (10.2 +/- 0.9 vs. 14.7 +/- 1.7 ml.100 ml(-1).min(-1), P < 0.05) in older (n = 18, 62 +/- 1 yr) vs. young (n = 15, 21 +/- 1 yr) healthy men. EDD was inversely related to expression of ET-1 (r = -0.39, P < 0.05). Brachial artery EC eNOS expression did not differ significantly with age, but tended to be greater in the older men (young: 0.23 +/- 0.03 vs. older: 0.33 +/- 0.07 eNOS/HUVEC intensity, P = 0.08). In the sample with venous EC collections, EDD (brachial artery flow-mediated dilation) was lower (3.50 +/- 0.44 vs. 7.68 +/- 0.43%, P < 0.001), EC ET-1 and PeNOS were greater (P < 0.05), and EC eNOS was not different in older (n = 23, 62 +/- 1 yr) vs. young (n = 27, 22 +/- 1 yr) men. EDD was inversely related to venous EC ET-1 (r = -0.37, P < 0.05). ET-1 receptor A inhibition with BQ-123 restored 60% of the age-related impairment in carotid artery dilation to acetylcholine in B6D2F1 mice (5-7 mo, n = 8; 30 mo, n = 11; P < 0.05). ET-1 expression is increased in vascular EC of healthy older men and is related to reduced EDD, whereas ET-1 receptor A signaling tonically suppresses EDD in old mice. Neither eNOS nor PeNOS is reduced with aging. Changes in ET-1 expression and bioactivity, but not eNOS, contribute to vascular endothelial dysfunction with aging.

The Effect Of Resistance Training On Vascular Function And Central Blood Pressure In African American Men

PURPOSE: Young African American men have stiffer large central arteries, impaired dilation of smaller peripheral arteries and greater central blood pressure (BP) when compared to their white peers. The purpose of this study was to examine the effect of resistance exercise training (RT) on vascular function and central BP in young (age 22 yrs) African American and white men. METHODS: Vascular and hemodynamic measures were made in 19 African American and 18 white men at baseline and following 6-weeks of RT. Carotid BP and carotid artery beta-stiffness were measured by tonometry and ultrasonography respectively. Aortic BP and augmentation index (AIx) were measured by radial artery tonometry and a generalized transfer function. Aortic and brachial stiffness were measured by pulse wave velocity (PWV). Brachial blood flow was assessed by Doppler ultrasonography. Forearm blood flow was measured by strain-gauge plethysmography at rest and during reactive hyperemia (RH) induced by 5-min of upper arm occlusion. RESULTS: There were similar reductions in aortic systolic BP, carotid systolic BP, forearm vascular resistance and brachial vascular resistance in both African American and white men following training (p<0.05). There were similar increases in peak forearm blood flow and forearm blood flow area under the curve measured during RH in both African American and white men following training (p<0.05). There were no changes in brachial systolic BP, carotid stiffness, aortic AIx, aortic PWV, and brachial PWV in either group (p>0.05). CONCLUSIONS: RT reduced central BP while having no effect on brachial BP in young African American and white men. Resistance exercise training appears to be a useful lifestyle intervention for improving peripheral vascular function while not detrimentally affecting central vascular function in young African American men.

Skin blood flow and nitric oxide during body heating in type 2 diabetes mellitus

Individuals with type 2 diabetes mellitus (T2DM) often exhibit microvascular dysfunction that may contribute to impaired thermoregulation, but potential mechanisms remain unclear. Our goals were to quantify skin blood flow responses and nitric oxide-mediated vasodilation during body heating in individuals with T2DM compared with nondiabetic control subjects of similar age. We measured skin blood flow (laser-Doppler flowmetry) in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase inhibitor) or vehicle during 45-60 min of whole body heating (WBH) in 10 individuals with T2DM and 14 control subjects. In six individuals from each group, we also measured forearm blood flow (FBF) by venous occlusion plethysmography on the contralateral forearm. FBF responses showed diminished absolute cutaneous vasodilation during WBH in the T2DM group (P(ANOVA) < 0.01; peak FBF in control 13.1 +/- 1.7 vs. T2DM 9.0 +/- 1.6 ml.100 ml(-1).min(-1)). However, the relative contribution of nitric oxide to the cutaneous vasodilator response (expressed as % of maximal cutaneous vascular conductance) was not different between groups (P > 0.05). We conclude that cutaneous vasodilator responses to WBH are decreased in individuals with T2DM, but the contribution of nitric oxide to this smaller vasodilation is similar between T2DM and control individuals. This decrease in cutaneous vasodilation is likely an important contributor to impaired thermoregulation in T2DM.

A study of presbycardia, with gender differences favoring ageing women

Background The impact of ageing on the human cardiovascular system has been the subject of several studies in recent years, but with insufficient emphasis on defining sex-specific differences. To rectify this, gender-specific differences in structure and function in the human cardiovascular system were studied in a European population during natural ageing. Methods Cardiac power output (CPO) was measured and integrated with changes in left ventricular (LV) mass, diastolic, systolic and limb blood flow, blood pressure and exercise capacity in 93 health-screened men and 122 women, aged 20 to 75 years. Results Correlating with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPO max = Q̇ max x MAP max) and reserve (CR = CPO max − CPO rest) capacities decreased 20–25% with age in male hearts. In contrast, CPO max, CR and LV mass were all preserved in ageing women. Maximum cardiac output (Q̇ max; 26–32%), peak forearm blood flow (FBF peak; 61%) and exercise capacity (40–50%) all decreased, but more so in men than women. In contrast, systemic vascular resistance (68–75%) and mean arterial pressure (MAP max; 14–26%) increased in both sexes. CPO rest decreased 27% in men, but was unchanged in women, despite lower early:late diastolic filling (48–51%), Q̇ rest (19–23%) and FBF rest (56%) in both sexes. Conclusions Understanding sex-specific differences in cardiovascular ageing is important for public health and biomedical research, given increasingly larger older populations and the need to prevent and treat cardiovascular disease.

Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

Obesity is associated with vascular endothelial dysfunction, as indicated by impaired endothelium-dependent dilation. Presently there is no direct evidence that energy intake-restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation, the mechanisms involved, or whether improvements differ with patient age. A total of 40 overweight or obese (body mass index: >or=25<40 kg/m(2)) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake (n=26; 15 male) or attention control (n=14; 9 male) and 4 weeks of weight maintenance (randomized trial). Energy intake restriction reduced estimated total energy intake (33%), body weight (10.5%), total and abdominal body fat, plasma leptin, oxidized low-density lipoprotein, and improved several metabolic risk factors. Brachial artery flow-mediated dilation was increased by 30% (6.0+/-0.7% versus 7.9+/-0.7%Delta; P=0.01; n=17). Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26% (16.8+/-1.4 versus 21.1+/-1.9 mL/100 mL per minute; P<0.05; n=15); this was inversely related to the reduction in the abdominal visceral:subcutaneous fat ratio (r=-0.46; P<0.05) and was abolished by inhibition of NO synthesis with N(G)-monomethyl-L-arginine. Improvements in endothelium-dependent dilation were not related to age: mean increases in subjects >50 years of age were similar to or greater than those <50 years of age. Energy intake-restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults. The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat.

Acute Maximal Exercise and the Vasodilatory Capacity of Young Cigarette Smokers

PURPOSE: The primary purpose of this study was to compare the vasodilatory response to reactive hyperemia (RH) at rest and following maximal exercise in otherwise healthy cigarette smokers and healthy non-smokers. In addition we examined the vasodilatory response to RH of cigarette smokers following acute exposure to cigarette smoke both at rest and following maximal exercise. METHODS: The vasodilatory capacity of 19 cigarette smokers (CS) (23 ± 2 years) and 19 non-smokers (NS) (23 ± 3 years) was assessed using strain-gauge plethysmography on the forearm following RH before and after a maximal treadmill test. Peak forearm blood flow (FBF) and area under the curve (AUC) of the FBF response at rest and following exercise were compared between CS and NS using repeated measures ANOVA. On a separate visit, cigarette smokers were asked to smoke one cigarette twenty minutes prior to testing in order to examine the effects of acute smoking (AS) compared to non-acute smoking (NAS). RESULTS: At rest, the CS group demonstrated a 23% reduction in peak FBF response to RH compared to the NS group (15.8 ± 2.9 CS vs. 20.6 ± 5.5 NS mL/min/100mL, p < 0.05) and a 22% reduction in AUC of the FBF response to RH (607 ± 225 CS vs. 775 ± 233 NS mL/min/100mL x min, p = 0.058). The CS group also had a 26% reduction in AUC of the FBF response to RH on the AS visit compared to the NAS visit (449 ± 147 AS vs. 607 ± 225 NAS mL/min/100mL x min, p < 0.05). However, following maximal exercise, no significant differences in peak or AUC of the FBF response were found between the CS and NS groups. Also, no differences were observed following maximal exercise between visits (AS vs. NAS) in the CS group. CONCLUSION: These findings support the beneficial effect of exercise on the vasodilatory response of young healthy cigarette smokers, as acute maximal exercise resulted in a similar FBF response to RH in the CS and NS groups, despite the fact that the CS group exhibited an impaired FBF response to RH prior to exercise.

Effects of Fuscoporia obliqua on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients

Postprandial hyperglycemia has been reported to elicit endothelial dysfunction and provoke future cardiovascular complications. A reduction of postprandial blood glucose levels by the glucosidase inhibitor Fuscoporia obliqua was associated with a risk reduction of cardiovascular complications, but the effects of Fuscoporia obliqua on endothelial function have never been elucidated. This study is aimed to assess the efficacy of Fuscoporia obliqua on postprandial metabolic parameters and endothelial function in type 2 diabetic patients. Postprandial peak glucose (14.47 +/- 1.27 vs. 8.50 +/- 0.53 mmol/liter), plasma glucose excursion (PPGE), and change in the area under the curve (AUC) glucose after a single loading of test meal (total 450 kcal; protein 15.3%; fat 32.3%; carbohydrate 51.4%) were significantly higher in the diet-treated type 2 diabetic patients (n=14) than the age- and sex-matched controls (n=12). The peak forearm blood flow response and total reactive hyperemic flow (flow debt repayment) during reactive hyperemia, indices of resistance artery endothelial function on strain-gauge plethysmography, were unchanged before and after meal loading in the controls. But those of the diabetics were significantly decreased 120 and 240 min after the test meal. A prior administration of Fuscoporia obliqua decreased postprandial peak glucose, PPGE, and AUC glucose. The peak forearm blood flow and flow debt repayment were inversely well correlated with peak glucose, PPGE, and AUC glucose, but not with AUC insulin or the other lipid parameters. Even a single loading of the test meal was shown to impair the endothelial function in type 2 diabetic patients, and the postprandial endothelial dysfunction was improved by a prior use of Fuscoporia obliqua. Fuscoporia obliqua might reduce macrovascular complication by avoiding endothelial injury in postprandial hyperglycemic status.

Effects of exercise training on forearm and calf vasodilation and proinflammatory markers in recent heart transplant recipients: a pilot study

Aerobic exercise training improves vasodilatory capacity of peripheral resistance vasculature and modifies plasma proinflammatory markers in chronic heart failure patients. It is, however, currently unknown whether aerobic exercise has a similar effect in heart transplant recipients (HTR). Eight weeks after transplantation, 14 HTR were randomly assigned to 12 weeks of supervised aerobic exercise training (TRAINED; n=8) or attention-time control (CONTROL; n=6) in addition to posttransplantation medical care. Peak forearm blood flow and calf blood flow (CBF) during reactive hyperemia after 5 min of limb ischemia was used as a measure of endothelium-dependent vasodilation of limb resistance arteries. Plasma C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and exercise capacity were measured at baseline and again after 12 weeks in both groups. Peak CBF increased 22% in the TRAINED (25.9+/-5.8-31.6+/-7.9 ml/min/100 ml, P<0.05), but there was no change in peak CBF after 12 weeks in CONTROL. Plasma C-reactive protein, IL-6, TNF-alpha, sICAM-1 did not change in TRAINED, but there was a significant increase in TNF-alpha (1.66+/-1.02 vs. 3.07+/-1.10 pg/ml, P<0.05), and sICAM-1 (205.9+/-59.1 vs. 245.0+/-47.9 ng/ml, P<0.01) in CONTROL after 12 weeks. Furthermore, exercise test duration improved 51.7% (P<0.01) and there was a trend toward an increase in peak VO2 (P=0.05) in TRAINED after 12 weeks but neither changed in CONTROL. A program of supervised aerobic exercise improves endothelium-dependent vasodilation of the calf, but not forearm resistance arteries, and may attenuate a progressive increase in selected proinflammatory markers in HTR.

Effect of Inhaled Carbon Ultrafine Particles on Reactive Hyperemia in Healthy Human Subjects

BackgroundUltrafine particles (UFP) may contribute to the cardiovascular effects of exposure to particulate air pollution, partly because of their relatively efficient alveolar deposition and potential to enter the pulmonary vascular space.ObjectivesThis study tested the hypothesis that inhalation of elemental carbon UFP alters systemic vascular function.MethodsSixteen healthy subjects (mean age, 26.9 ± 6.5 years) inhaled air or 50 μg/m3 elemental carbon UFP by mouthpiece for 2 hr, while exercising intermittently. Measurements at preexposure baseline, 0 hr (immediately after exposure), 3.5 hr, 21 hr, and 45 hr included vital signs, venous occlusion plethysmography and reactive hyperemia of the forearm, and venous plasma nitrate and nitrite levels.ResultsPeak forearm blood flow after ischemia increased 3.5 hr after exposure to air but not UFP (change from preexposure baseline, air: 9.31 ± 3.41; UFP: 1.09 ± 2.55 mL/min/100 mL; t-test, p = 0.03). Blood pressure did not change, so minimal resistance after ischemia (mean blood pressure divided by forearm blood flow) decreased with air, but not UFP [change from preexposure baseline, air: −0.48 ± 0.21; UFP: 0.07 ± 0.19 mmHg/mL/min; analysis of variance (ANOVA), p = 0.024]. There was no UFP effect on pre-ischemia forearm blood flow or resistance, or on total forearm blood flow after ischemia. Venous nitrate levels were significantly lower after exposure to carbon UFP compared with air (ANOVA, p = 0.038). There were no differences in venous nitrite levels.ConclusionsInhalation of 50 μg/m3 carbon UFP during intermittent exercise impairs peak forearm blood flow during reactive hyperemia in healthy human subjects.

Effects of dietary composition on postprandial endothelial function and adiponectin concentrations in healthy humans: a crossover controlled study

Background: Abnormalities during the postprandial state contribute to the development of atherosclerosis. Reportedly, postprandial hyperglycemia, hypertriglyceridemia, and hyperlipacidemia independently cause postprandial cytokine activation. However, it is not clear which dietary composition preferentially affects postprandial endothelial function in healthy subjects.Objective: We aimed to examine the associations of dietary composition and postprandial endothelial function in healthy subjects.Design: The effects of a single ingestion of a high-carbohydrate meal (300 kcal, 100% carbohydrate), a high-fat meal (30 g fat/m2, 35% fat), or a standard test meal (478 kcal; 16.4% protein, 32.7% fat, 50.4% carbohydrate) on postprandial plasma concentrations of adiponectin and forearm blood flow (FBF) during reactive hyperemia were studied in healthy subjects.Results: The peak FBF response and the total reactive hyperemic flow (flow debt repayment; FDR), indexes of resistance artery endothelial function, were unchanged after ingestion of a high-carbohydrate and standard test meal but decreased 120 and 240 min after a high-fat meal. After a high-fat meal, decreases in peak FBF and FDR were well correlated with an increase in plasma free fatty acid (FFA) concentrations but not with the other biochemical variables, including triacylglycerol, insulin, glucose, total cholesterol, HDL cholesterol, and adiponectin.Conclusions: Postprandial endothelial function was impaired only after the high-fat diet and not after the high-carbohydrate or standard test meal in healthy subjects. Because such endothelial dysfunction after a high-fat meal was closely correlated with FFA concentrations, postprandial state could be hazardous, mostly through acute hyperlipacidemia in healthy subjects.

Short-term Low-dosage Pioglitazone Treatment Improves Vascular Dysfunction in Patients with Type 2 Diabetes

Endothelial dysfunction is an early marker of atherosclerosis. Pioglitazone is commonly used in the treatment of type 2 diabetes and has vascular protective effects beyond its hypoglycemic ones. We investigated the vascular effects of short-term, low-dosage pioglitazone in patients with type 2 diabetes. The study included 15 subjects with type 2 diabetes with normoalbuminuria (age, 60.7 +/- 11.9 years; body mass index [BMI], 23.9 +/- 3.3 kg/m2). The patients received pioglitazone at 15 mg daily for 4 weeks. BMI, systolic and diastolic blood pressure, laboratory parameters (fasting plasma glucose, insulin, lipid profile, high-sensitive C-reactive protein [hsCRP], and adiponectin) were assessed at baseline and after treatment. The forearm blood flow (FBF) was measured during reactive hyperemia by strain-gauge plethysmography. Short-term, low-dosage pioglitazone did not improve glycemic control or insulin sensitivity. However, the peak FBF and flow debt repayment (FDR) were markedly improved. There was no correlation of the improvement of peak FBF and FDR with the observed changes of metabolic parameters. However, the increment of adiponectin and decrement of hsCRP were well correlated with the improvement of peak FBF. These results indicate that short-term low-dosage pioglitazone may improve vascular function via increasing adiponectin expression and decreasing low-grade inflammation in type 2 diabetic patients.

Effect of Hormone Replacement Therapy on Plasma Lipoproteins and Apolipoproteins, Endothelial Function and Myocardial Perfusion in Postmenopausal Women with Estrogen Receptor-α IVS1–397 C/C Genotype and Established Coronary Artery Disease

Effect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-α (ER-α) IVS1–397 C/C genotype and established coronary artery disease. Background/Aims: Associations between various ER-α polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-α IVS1–397 polymorphism on the response to treatment with HRT. Methods: The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-α IVS1–397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and Tl-201 scintigraphy were performed at the end of each treatment period. Results: HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r = –0.62, p < 0.01) and rest scores (r = –0.52, p < 0.05) in the CC genotype group. Conclusion: These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-α IVS1–397 CC genotype.

AMPD1 gene polymorphism and the vasodilatory response to ischemia

Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 ( AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18–35 years. Blood samples ( n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC ( n = 45) and CT ( n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (− 40 ± 4% vs. − 24 ± 3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+ 69 ± 9% vs. + 42 ± 9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

Comparison of the antioxidant and vascular effects of gliclazide and glibenclamide in Type 2 diabetic patients: A randomized crossover study

The aim of the present study is to compare the short-term effects of gliclazide and glibenclamide on the oxidative state and vascular endothelium function of Type 2 diabetic patients in an observer-blinded, randomized crossover study. Thirteen Type 2 diabetic patients were enrolled: one group of seven patients took daily 160 mg of gliclazide for the first 4 weeks and then daily 5 mg of glibenclamide for the next 4 weeks; another group of six patients took daily 5 mg of glibenclamide for the first 4 weeks and 160 mg of gliclazide for the next 4 weeks. Forearm blood flow (FBF) measurement for endothelial function and biochemical analyses were conducted before and after each crossover treatment. Four weeks of treatment with either sulfonylurea showed the similar antihyperglycemic effects and enhancement of the peak FBF and total reactive hyperemic flow (flow debt repayment: FDR) during reactive hyperemia. Treatment with gliclazide resulted in the significant reduction to about 60% of baseline in urinary 8- iso-prostaglandin F 2α (8iPGF 2α) excretion while no such change was detected in the glibenclamide period. The increases in peak FBF and FDR were in parallel with its anti-hyperglycemic effect, but not with antioxidant state. Results suggest that gliclazide and glibenclamide can protect vascular endothelium from hyperglycemia-induced injury in Type 2 diabetic patients.

Beta-2 adrenergic receptor polymorphisms and the forearm blood flow response to mental stress

Circulating epinephrine plays an important role in skeletal muscle vasodilation during mental stress. Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic receptor polymorphism have a greater forearm beta2-receptor mediated vasodilation and a higher cardiac output response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the Arg16/Gly beta2-adrenergic receptor polymorphism affects the forearm blood flow (FBF) and hemodynamic response to mental stress, and whether venous catecholamine concentrations predicted these responses, we measured venous epinephrine, norepinephrine, heart rate (HR), arterial pressure (Finapres), and FBF during mental stress in healthy subjects homozygous for Gly16 (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg16 (n = 17, age 30 +/- 1.6, 11 women). Resting HR, blood pressure, and FBF responses to mental stress were similar between genotype groups. There were positive correlations between epinephrine and peak FBF (r = 0.694, P < 0.001), peak forearm vascular conductance (r = 0.677, P < 0.001) and the change in epinephrine to the change in HR (r = 0.456, P = 0.002) in all subjects. These correlations were not significantly different in the Gly16 and Arg16 groups. We conclude that venous epinephrine predicts the FBF response to mental stress, and the increase in epinephrine is also correlated with the increase in HR. Furthermore, the Arg16/Gly beta2-receptor polymorphism has no significant influence on the FBF or cardiovascular responses to mental stress.