THE EFFECT OF INSULIN ON THE VASCULAR REACTIVITY OF ISOLATED RESISTANCE ARTERIES TAKEN FROM HEALTHY-VOLUNTEERS

Impaired reactivity of the resistance vasculature may contribute to th e development of diabetic microangiopathy by altering microvascular ha emodynamics. This study investigates the acute effects of insulin on t he contractility and relaxation properties of isolated human resistanc e arteries (< 300 mu m internal diameter) taken from gluteal subcutane ous fat of 33 (18 male: 15 female) normotensive healthy volunteers (su pine blood pressure 115.6 +/- 1.6/70.0 +/- 1.5 mm Hg [mean +/- SEM], w ith no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after in cubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increas ing concentrations of insulin were found to reduce the contractile res ponse to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8 % [p < 0.01], 1 mU/ml by 17 % [p < 0.02] and 10 mU/ml by 22 % [p < 0.01]). Sensitivity to insulin (ED(50)) only decreased at the highes t concentration of insulin. However, acetycholine-induced relaxation w as not altered by insulin (Group 2). Time control studies (Group 3) sh owed that contractile and relaxation responses over the 4-h study peri od were unchanged. Furthermore, the length of time the vessels were ex posed to insulin did not progressively impair responses (Group 4). The se findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacer bate the abnormal haemodynamics observed in the capillary microcircula tion of numerous vascular beds in diabetes.