SELECTIVE ENHANCEMENT OF ALPHA(2)-ADRENOCEPTOR-MEDIATED VASOCONSTRICTION IN INSULIN-DEPENDENT DIABETIC-PATIENTS WITH MICROALBUMINURIA

1. Microalbuminuria, the earliest clinical marker of microvascular dis ease, is an important predictor of early death in insulin-dependent di abetes, and abnormal vascular reactivity may contribute to microvascul ar disease. We have previously found that vasoconstrictive responses t o noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin- dependent diabetic patients and non-diabetic control subjects. 2. To d etermine whether this is due to increased sensitivity at alpha(1)- or alpha(2)-adrenergic receptors, we compared vascular responses to the a lpha(1)-adrenergic agonist phenylephrine and the alpha(2)-adrenergic a gonist clonidine.3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with nor mal urinary albumin excretion and 14 non-diabetic subjects. Vascular c onstrictive responses were measured in dorsal hand veins. 4. No differ ence in vasoreactivity to phenylephrine was demonstrated between any o f the three groups. However, enhanced vascular responsitivity to cloni dine at infusion rates of 16-2048 ng/min (analysis of variance, P<0.00 1) was found in insulin-dependent diabetic patients with microalbuminu ria as compared with both non-diabetic control subjects and normoalbum inuric insulin-dependent diabetic patients. There were no significant differences between the dose-response curves of the diabetic group wit h normal urinary albumin excretion and the non-diabetic group. 5. Vaso constriction mediated by alpha(2)-adrenergic receptors is therefore en hanced in normotensive insulin-dependent diabetic patients with microa lbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to s ystemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.