INHIBITION OF NITRIC-OXIDE SYNTHESIS IN FOREARM VASCULATURE OF INSULIN-DEPENDENT DIABETIC-PATIENTS - BLUNTED VASOCONSTRICTION IN PATIENTS WITH MICROALBUMINURIA

1. Microalbuminuria is a risk factor for cardiovascular disease in pat ients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose o f this study was to determine whether vasoconstrictor responses to N(G )-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty -eight insulin-dependent diabetic patients (14 with normal albumin exc retion, 14 with microalbuminuria) were studied under euglycaemic condi tions, together with 14 healthy control subjects. Forearm vascular res ponses to brachial artery infusions of N(G)-monomethyl-L-arginine, sod ium nitroprusside (an endothelium-independent nitrovasodilator) and ca rbachol (an endothelium-dependent vasodilator) were determined by stra in gauge plethysmography. 3. Basal blood flow and vasodilator response s were similar in each group. N(G)-Monomethyl-L-arginine reduced blood flow by 41.3+/-2.3% (mean+/-SEM) in healthy control subjects, 34.0+/- 3.4% in diabetic patients without microalbuminuria and 29.2+/-2.0% in diabetic patients with microalbuminuria. Diabetic patients differed fr om healthy subjects (P=0.005), due to a difference between control sub jects and microalbuminuric diabetic patients (P<0.001). N(G)-Monomethy l-L-arginine did not influence nitroprusside responses but reduced car bachol responses in control subjects and normoalbuminuric diabetic pat ients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitri c oxide biosynthesis in insulin-dependent diabetic patients with micro albuminuria.