Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension B. Z Ï IZ Ï EK & P. POREDOS Ï From the Department of Angiology, University Medical Centre, Ljubljana, Slovenia Abstract. Z Ï iz Ïek B, Poredos Ï P (University Medical Centre, Ljubljana, Slovenia). Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension. J Intern Med 2001; 249: 189±197. Objectives. To evaluate whether endothelium- dependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between ¯ow- mediated vasodilation (FMD) and hyperinsulina- emia/insulin resistance. Design. Cross-sectional study. Setting. Angiology department at a teaching hospi- tal. Subjects. The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40±55 (49) years, and 44 age-matched, normotensive volun- teers as controls. We also investigated 41 normo- tonics with FT aged 20±30 (25) years and 41 age-and sex-matched controls without FT. Main outcome measures. Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. Results. In hypertonics FMD was signi®cantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P  0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was compar- able in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). Conclusions. In treated patients with EH, ¯ow-me- diated dilation of the BA as well as endothelium- independent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications. Keywords: dilation of conduit arteries, endothelial dysfunction, essential hypertension, hyperinsulina- emia. Introduction Essential arterial hypertension (EH) is an important risk factor for atherosclerosis. Pathomorphological changes of the arterial wall, which are related to the blood pressure levels and to the duration of elevated blood pressure, are well-known consequences of hypertension [1]. The appearance of functional abnormalities of the arterial wall in hypertensive disease is not well understood. There is growing evidence that endothelial dysfunction with impair- ment of vasodilatation is the earliest event in atherogenesis, and also precedes morphological changes of the arterial wall in hypertensive patients [2±4]. Journal of Internal Medicine 2001; 249: 189±197 ã 2001 Blackwell Science Ltd 189