Prostaglandins and nitric oxide mediate insulin-induced vasodilation in the human forearm

OBJECTIVE: To determine the involvement of prostaglandins, nitric oxide, and beta-adrenoceptor activation in insulin-induced vasodilation in the human forearm. METHODS: Fifteen normal subjects were studied. Insulin was administered into the brachial artery in the presence of saline, the cyclo-oxygenase inhibitor indomethacin (0.65 microgram/kg/min), the inhibitor of nitric oxide synthase NG-mono-methyl-L-arginine (L-NMMA, 30 micrograms/kg/min), or the non-selective beta-adrenoceptor blocker propranolol (0.2 microgram/kg/min). Forearm vascular resistance (FVR) was derived from forearm blood flow and concomitantly measured intra-arterial blood pressure. RESULTS: Insulin decreased FVR by 32 +/- 5% (P < 0.01). Both indomethacin and L-NMMA inhibited insulin-induced vasodilation, while propranolol had no effect. Single infusion of indomethacin was without effect on vascular tone, while single infusion of L-NMMA increased FVR by 81 +/- 19% (P < 0.01). CONCLUSIONS: Insulin has vasodilating properties in skeletal muscle vasculature that is mediated by increases in nitric oxide, that subsequently stimulates prostaglandin release. The latter appears to be a novel vascular action of insulin.