Abstract 2527: Impairment Of Insulin-stimulated Vasodilation In Patients With Metabolic Syndrome
Defective vasorelaxation is one of the earliest abnormalities in the atherosclerotic process. Insulin has previously been shown to enhance endothelium-dependent vasodilator responsiveness, therefore a defect in this mechanism may predispose to increased atherosclerotic risk in clinical conditions associated with insulin resistance. In our study, we tested the hypothesis that impaired insulin-stimulated vasodilation may be present in the arteries of insulin resistant patients with obesity-related metabolic syndrome (MetS; ATP III criteria). To this aim, forearm blood flow responses to graded doses of acetylcholine (ACh; 7.5, 15 and 30 μg/min), a stimulus for endothelial release of nitric oxide (NO), and sodium nitroprusside (SNP; 0.8, 1.6 and 3.2 μg/min), an exogenous NO donor, were assessed by strain-gauge plethysmography in patients with MetS (n=20) and in matched controls (n=18), before and after intra-arterial infusion of insulin (0.2 mU/Kg/min). In control subjects, a significant potentiation of the vasodilator responses to both ACh and SNP was obsereved after insulin infusion (both P=0.003 vs. before). By contrast, no significant difference in the vasodilator responses to ACh and SNP was observed following hyperinsulinemia in patients with MetS (P=0.56 and P=0.86, respectively, vs. before). To ascertain whether the abnormal insulin-stimulated vasodilation of MetS is limited to NO-dependent stimuli, the effect of insulin on the vasodilator response to verapamil, a calcium-channel blocker acting through NO-independent mechanisms, was also examined in both groups. Again, a significant enhancement of verapamil-induced vasodilation was observed following insulin administration in controls (P=0.003), but not in patients with MetS (P=0.28). In conclusion, our data indicate that patients with obesity-related MetS have generalized impairment in insulin-stimulated vasodilator responsiveness, likely due to defective insulin signaling in vascular smooth muscle cells affecting the facilitatory effect of insulin on relaxation. Given the importance of impaired vasodilator function in subsequent vascular damage, this defect may then contribute to the development of vascular complications in insulin resistant states.