Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m 2 ), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 µg · ml -1 · min -1) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 µg · ml -1 · min 19.8 ± 2.8, 10.8 ± 2.7, and 6.5 ± 1.8 ml · 100 ml -1 tissue · min -1 (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity. O bese subjects are at high risk for developing diabetes, dyslipidemia, hypertension, and cardiovascular diseases, which lead to an increased risk of mortality (1-3). Moreover, it has been demonstrated that obesity is associated with hyperinsulinemia, an independent predictor for coronary artery disease (4). In fact, hyperinsulinemia is linked to insulin resistance (IR) and potentially to atherogenic abnormalities.The normal endothelium plays a key role in the regulation of vascular tone and in preventing the progression of atherosclerosis through the production and release of both contracting and relaxing factors (5). Nitric oxide (NO) represents the major endogenous relaxing factor (6-9), and its production is stimulated by physical stimuli (e.g., shear stress) (9) and by several agonists (e.g., acetylcholine [ACh], bradykinin, substance P, and serotonin) (8). The activation of guanylate cyclase and the subsequent accumulation of cGMP are the main mechanisms of NO-induced vasodilation. In contrast, sodium nitroprusside (SNP) is an endothelium-independent vasodilator capable of inducing vasodilation by providing an inorganic source of NO (10). Major risk factors for atherosclerotic vascular diseases (e.g., hypertension, smoking, diabetes, and hypercholesterolemia) have been associated with endothelial dysfunction due to increased oxidative stress (11-16). Recent reports have also indicated tha...

Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.

The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.

Abstract-The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityϫblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressureϫinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6Ϯ3.3 dynes/cm 2 (meanϮSD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4Ϯ0.6ϫ10 4 dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (rϭ0.55, PϽ0.0001) and directly associated with circumferential wall tension (rϭ0.43, PϽ0.0001). Shear stress and circumferential wall tension were inversely correlated (rϭ0.66, PϽ0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors. (Hypertension. 1999;34:217-221.) Key Words: carotid arteries Ⅲ atherosclerosis Ⅲ stress, mechanical Ⅲ tensile stress Ⅲ tunica media A therosclerosis is a systemic disease, caused or favored by systemic risk factors, that localizes in particular regions of the arterial tree, probably through interaction with local predisposing factors. 1-2 Among the predisposing factors, the hemodynamic forces (shear stress and tensile stress) generated by flowing blood are of utmost importance. [3][4][5][6] Shear stress is the frictional force that acts tangentially to the endothelial surface. Tensile stress is the circumferential wall tension divided by wall thickness, and it acts perpendicularly to the arterial wall and results from the extensional (dilating) effect of blood pressure on the vessel. These hemodynamic forces also influence the vessel wall structure and development and contribute to the regulation of vascular tone. 5,[7][8][9][10][11] In vitro and in vivo experiments have demonstrated that vessels tend to maintain constant shear stress in response to flow changes. [12][13][14] We have previously demonstrated that common carotid artery shear stress in healthy men in vivo decreases with increasing age, blood pressure, and body mass index (BMI) and that low shear stress values are associated with intima-media thickening, an ech...

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