Background-Insulin resistance is often accompanied by hyperinsulinemia and may predispose to atherosclerosis.Endothelium plays a central role in atherogenesis. The in vivo effects of hyperinsulinemia on endothelial function of large conduit arteries are unknown. Methods and Results-Twenty-five healthy subjects were enrolled for study. In study A (nϭ9), subjects underwent both a time-control saline study and a euglycemic low-dose insulin (insulin Ϸ110 pmol/L) clamp for 6 hours. Study B (nϭ5) was identical to study A except that the euglycemic clamp was performed at high physiological insulin concentrations (Ϸ440 pmol/L). In study C (nϭ7), subjects underwent two 4-hour euglycemic insulin (Ϸ110 pmol/L) clamps with and without the concomitant infusion of an antioxidant (vitamin C). In study D (nϭ4), two saline time-control studies were performed with and without the concomitant infusion of vitamin C. In all studies, both at baseline and throughout the experimental period, endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-induced) vasodilation was assessed in femoral and brachial arteries by echo Doppler. Both low (study A) and high physiological (study B) hyperinsulinemia abolished endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was unaffected. Vitamin C fully restored insulin-impaired endothelial function without affecting endotheliumindependent vasodilation (study C). Vitamin C had no effects on endothelium-dependent or endothelium-independent vasodilation during saline control studies (study D). Conclusions-Modest hyperinsulinemia, mimicking fasting hyperinsulinemia of insulin-resistant states, abrogates endothelium-dependent vasodilation in large conduit arteries, probably by increasing oxidant stress. These data may provide a novel pathophysiological basis to the epidemiological link between hyperinsulinemia/insulin-resistance and atherosclerosis in humans. (Circulation. 2002;105:576-582.)

OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional andaor structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was signi®cantly impaired in obese subjects (P`0.005 versus non-obese subjects) while glyceril-trinitrate vasodilation and arterial distensibility were similar in the two groups. In our obese subjects endothelial-dependent vasodilation was inversely correlated to body fat distribution (visceralasubcutaneous adipose tissue ratio: r À0.624, P 0.0058). In contrast, metabolic parameters (except C-peptide response during oral glucose tolerance test (OGTT): r À0.587, P 0.01), blood pressure values and body weight did not correlate with the endothelial function. CONCLUSION: Uncomplicated obesity per se is characterised by an alteration of the endothelial function; the degree of this vascular damage is predicted by body fat distribution independently of body weight and metabolic and other haemodynamic parameters, and correlates with an index of insulin secretion.

Abstract. Pancera P, Ribul R, Presciuttini B, Lechi A (Universita Á di Verona, Italy). Prevalence of carotid artery kinking in 590 consecutive subjects evaluated by Echocolordoppler. Is there a correlation with arterial hypertension? J Intern Med 2000; 248: 7±12.Objective. To assess a possible correlation between high blood pressure and prevalence of kinking in carotid arteries. Design. Between July 1, 1997 and December 31, 1998, we evaluated the subjects submitted to Echocolordoppler examination of carotid arteries. Setting. Patients were examined at the Laboratory for Noninvasive Vascular Diagnostics of the University Hospital in Verona. Subjects.F ratio, 1/1.2; mean age, 67 years; range, 36±86 years). Main outcome measures. An Echocolordoppler ultrasonograph to evaluate by means of the standard longitudinal and transverse scans the usual parameters of both intima-to-lumen interface and flow.Moreover, particular attention was paid to the analysis of the conformational characteristic of the vessels. Kinking has been classified in three classes according to the degree of bending. All the subjects were asked to compile a questionnaire that provided us with the clinical history.Results. The prevalence of hypertension in the subjects with kinking appeared higher than in subjects without this abnormality (x 2 = 6.44, P , 0.02). We found also a significant association between kinking and transitory ischaemic attacks (x 2 = 6.987, P , 0.01). Conclusions. The high prevalence of kinking in the hypertensives agrees with the pathogenetical hypothesis ascribing a role to the high endoluminal pressure. The presence of hypertension and kinking of the internal carotid artery suggests that they could be additive risk factors in the pathophysiology of a transitory ischaemic attack.

Background-Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system. Methods and Results-We measured the urinary excretion of 8-iso-prostaglandin (PG) F 2␣ and 11-dehydro-thromboxane (TX) B 2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF 2␣ was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB 2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF 2␣ correlated with 11-dehydro-TXB 2 (r s ϭ0.