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Abstract: Background: It is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Recently, we developed a new noninvasive method for measurement of vascular response to reactive hyperemia in the brachial artery, named enclosed zone flow-mediated vasodilation (ezFMD). The purpose of this study was to determine the validity of ezFMD for assessment of endothelial function. Methods and results: We measured ezFMD by a new device using an oscillometric method and conventional FMD using ultrasonography in 306 subjects, including patients with hypertension, dyslipidemia, and diabetes mellitus (218 men and 88 women, 30 ± 16 yr). Univariate regression analysis revealed that ezFMD significantly correlated with age (r = −0.42, P < 0.0001), body mass index (r = −0.13, P = 0.028), systolic blood pressure (r = −0.15, P = 0.009), diastolic blood pressure (r = −0.14, P = 0.011), fasting glucose level (r = −0.27, P = 0.006), smoking (r = −0.21, P = 0.007) and baseline pulse wave amplitude (r = −0.51, P < 0.0001). ezFMD significantly correlated with conventional FMD (r = 0.34, P < 0.0001). Multiple regression analysis revealed that age (P = 0.002), body mass index (P = 0.013), systolic blood pressure (P = 0.009), smoking (P = 0.004) and baseline pulse wave amplitude (P < 0.001) were independent predictors of ezFMD. Conclusions: These findings suggest that measurement of ezFMD, a novel noninvasive and simple method, may be useful for determination of vascular diameter response to reactive hyperemia. Since ezFMD is automatically measured by a device with an oscillometric method, measurement of ezFMD is easier and less biased than that of conventional FMD. [Copyright &y& Elsevier]

Abstract: A 51-year-old man recently diagnosed with preclinical Cushing's syndrome complained of chest oppression concomitant with back pain. Following contrast-enhanced computed tomography (CT) to rule out acute aortic dissection, he developed chest symptoms accompanied by elevation of blood pressure to 240/120mmHg and ischemic electrocardiographic change. Urgent coronary angiography revealed a coronary artery aneurysm (15mm×6mm) in the distal portion of the left anterior descending artery concomitant with coronary flow delay. Re-analysis of the blood sample taken at admission showed elevated plasma catecholamine concentrations, leading to a diagnosis of paroxysmal pheochromocytoma. An adrenal tumor was excised laparoscopically and histologically shown to be a pheochromocytoma. These findings show that coronary artery aneurysm may be a rare complication of pheochromocytoma, and indicate that monitoring of blood pressure or analysis of stored blood samples, if necessary, is essential to detect pheochromocytoma when using contrast medium or glucagon in patients known to have an adrenal incidentaloma. It should be noted that pre-treatment with an α-blocker is necessary when patients who are likely to have pheochromocytoma need to undergo contrast-enhanced CT. [Copyright &y& Elsevier]

Abstract: Background: Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor. Methods and results: We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30μg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97±0.37 vs. 0.51±0.14; P =0.002). Fasudil increased FBF from 4.9±1.2 to 14.5±5.7mL/min/100mL tissue (P <0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r =0.72, P <0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r =0.59, P <0.0001). In healthy subjects, there was no significant correlation between the two parameters. Conclusions: These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to determine pioglitazone treatment restores endothelial function in hypertensive patients with impaired glucose tolerance (IGT). Methods and results: We evaluated the effects of pioglitazone treatment for 12 weeks on forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside in 34 hypertensive patients with IGT who were randomly divided into a pioglitazone group (n =17) and an amlodipine monotherapy group (n =17) and in 34 healthy subjects. Pioglitazone, but not amlodipine, increased the FBF response to acetylcholine and decreased urinary excretion of 8-hydroxy-2′-deoxyguanosine. Pioglitazone did not alter sodium nitroprusside-stimulated vasodilation. N G -monomethyl-l-arginine abolished the augmentation of FBF response to acetylcholine after pioglitazone treatment. The increase in maximal FBF response to acetylcholine correlated with the decrease in urinary excretion of 8-hydroxy-2′-deoxyguanosine. Conclusion: Pioglitazone improved endothelial function in hypertensive patients with IGT through an increase in nitric oxide bioavailability by, in part, a decrease in oxidative stress. [Copyright &y& Elsevier]

Abstract: Objective: Several studies have shown that periodontitis is a risk factor for cardiovascular diseases. There is an association between inflammation and endothelial dysfunction. The purpose of this study was to evaluate endothelial function in patients with coronary artery disease (CAD) who had periodontitis. Methods and results: We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients with periodontitis (37 men and 11 women, 63±12 yr) and without periodontitis (36 men and 17 women, 62±13 yr). FBF was measured by using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the non-periodontitis group. FBF response to ACh was significantly smaller in the periodontitis group than in the non-periodontitis group. SNP-stimulated vasodilation was similar in the two groups. Periodontal therapy reduced serum concentrations of C-reactive protein from 2.7±1.9 to 1.8±0.9mg/L (P <0.05) and interleukin-6 from 2.6±3.4 to 1.6±2.6ng/L (P <0.05) and augmented ACh-induced vasodilation from 14.7±5.2 to 20.1±6.1mL/(min100mL) tissue (P <0.05) in patients with periodontitis. The SNP-stimulated vasodilation was similar before and after treatment. After administration of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, FBF response to ACh was similar before and after treatment. Conclusion: These findings suggest that periodontitis is associated with endothelial dysfunction in patients with CAD through a decrease in nitric oxide bioavailability. Systemic inflammation may be, at least in part, a cause and predictor of progression of endothelial dysfunction. [Copyright &y& Elsevier]