IMPAIRED NITRIC OXIDE-MEDIATED VASODILATION IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Objectives. This study sought to determine whether nitric oxide-mediat ed vasodilation is abnormal in patients with non-insulin-dependent dia betes mellitus. Background. Multiple investigations, both in experimen tal models and in patients with insulin-dependent diabetes mellitus, d emonstrate impaired endothelium-dependent vasodilation, Decreased avai lability of endothelium-derived nitric oxide may contribute to the hig h prevalence of vascular disease in diabetes. Methods. Vascular reacti vity was measured in the forearm resistance vessels of 21 patients wit h non-insulin-dependent diabetes mellitus and 23 matched healthy contr ol subjects, No patient had hypertension or hypercholesterolemia. Each subject was pretreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 mu g/min) was administered through a brachial artery cannula to assess vasodilat ion to endothelium derived nitric oxide, Sodium nitroprusside (0.3 to 10 mu g/min) was infused to evaluate vasodilation to an exogenous nitr ic oxide donor,Verapamil (10 to 300 mu g/min) was administered to dist inguish impaired nitric oxide-mediated vasodilation from general dysfu nction of vascular smooth muscle, Forearm blood how was determined by venous occlusion plethysmography, and dose-response curves were genera ted for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment. Results. Basal forearm blood how in diabetic and n ondiabetic subjects was comparable, The forearm blood how responses to both methacholine chloride and nitroprusside were significantly atten uated in diabetic compared with nondiabetic subjects (p < 0.005 by ana lysis of variance for both agents), In contrast, the response to verap amil was not significantly different between the groups (p > 0.50). Th e forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition. Conclusions. Nitric oxide-media ted vasodilation is impaired in non-insulin-dependent diabetes mellitu s. Vasoconstrictor prostanoids do not contribute significantly to vasc ular dysfunction, The attenuated response to exogenous as well as endo genous nitric oxide donors suggests that the abnormality is due to inc reased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide.