PLASMA ENDOTHELIN LEVELS AND VASCULAR EFFECTS OF INTRAVENOUS L-ARGININE INFUSION IN SUBJECTS WITH UNCOMPLICATED INSULIN-DEPENDENT DIABETES-MELLITUS

1. Uncomplicated insulin-dependent diabetes mellitus is associated wit h generalized vasodilatation. This vasodilatation is believed to contr ibute to the development of microvascular complications. The endotheli um plays an important role in the regulation of vascular tone. 2. To i nvestigate the role of endothelial mediators, we measured plasma endot helin levels and studied the vascular effects of intravenous L-arginin e (the precursor of NO) in 10 male type 1 diabetic patients and 10 non -diabetic subjects. 3. The baseline plasma endothelin level was signif icantly lower in the diabetic patients [mean 1.7(SD 0.5) versus 2.1(0. 4)pmol/l; P<0.05] than in the control subjects. 4. During L-arginine i nfusion, plasma cyclic GMP (the second messenger for NO) increased in the control subjects [from 5.1(2.9) to 6.9(2.9)nmol/l; P<0.05 versus s aline] and in the diabetic patients [from 4.6(1.8) to 5.7(2.2)nmol/l; P=0.09]. L-Citrulline (a by-product of NO synthesis from L-arginine) i ncreased in both groups. The responses to L-arginine were not signific antly different between the control subjects and the diabetic patients . The plasma atrial natriuretic peptide level did not change in either group during infusion of L-arginine or of an equal volume of isotonic saline. 5. Blood pressure decreased slightly during L-arginine admini stration in both groups. In control subjects, the extracellular fluid volume in the lower leg increased during L-arginine infusion as compar ed with saline; in the diabetic patients both L-arginine and saline in creased the extracellular fluid volume. 6. In conclusion, the vascular effects of L-arginine are similar in men with uncomplicated insulin-d ependent diabetes mellitus and in control subjects. Whether these effe cts are due to an increase in NO synthesis remains unclear. The increa se in extracellular fluid volume during saline infusion in diabetic pa tients suggests an increase in microvascular permeability in the basal state. The role of the lower plasma endothelin level in the vasodilat ation and capillary hypertension characteristic of uncomplicated insul in-dependent diabetes mellitus remains to be determined.