Selective enhancement of alpha 2-adrenoceptor-mediated vasoconstriction in insulin-dependent diabetic patients with microalbuminuria

Abstract

1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to 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 determine whether this is due to increased sensitivity at alpha 1- or alpha 2-adrenergic receptors, we compared vascular responses to the alpha 1-adrenergic agonist phenylephrine and the alpha 2-adrenergic agonist clonidine. 3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins. 4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16-2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin-dependent diabetic patients. There were no significant differences between the dose-response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group. 5. Vasoconstriction mediated by alpha 2-adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.