Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes

Abstract

Patients with insulin-dependent diabetes mellitus have an increased mortality and morbidity due to vascular complications. Nitric oxide from the vascular endothelium contributes to the control of normal vascular tone, and endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disease. In this study we have examined basal and stimulated nitric oxide-mediated vasodilatation in insulin-dependent diabetics and age- and sex-matched healthy controls. Drugs were infused locally into the brachial artery and forearm blood flow measured using venous occlusion plethysmography. Noradrenaline and NG-monomethyl-L-arginine produced similar reductions in resting forearm blood flow in healthy controls. However, in the diabetics, NG-monomethyl-L-arginine was significantly less effective than noradrenaline. Comparing between groups, the response to NG-monomethyl-L-arginine was also significantly less in the diabetics compared with the healthy controls. The response to sodium nitroprusside was significantly less in the diabetics compared with the healthy controls, whereas the responses to both acetylcholine and verapamil were the same in the two groups. The results provide evidence for an abnormality of basal nitric oxide-mediated dilatation in the forearm arterial bed of patients with insulin-dependent diabetes mellitus, and suggest that the vascular smooth muscle is less sensitive to nitric oxide.