N(G)-monomethyl-L-arginine alters insulin-mediated calf blood flow but not glucose disposal in the elderly.

It has been proposed that an important component of glucose disposal is insulin-mediated vasodilation via a nitric oxide (NO)-dependent mechanism. Normal aging is characterized by a resistance to insulin-mediated glucose disposal and deficient endothelial NO production. Impairment of insulin-mediated vasodilation could contribute to this insulin resistance. We tested the hypothesis that the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) would decrease insulin-mediated calf vasodilation and whole-body glucose disposal in young subjects but would have little or no effect in the elderly. Experiments were performed on healthy young (n = 10) and old (n = 10) subjects on 2 study days. Insulin was infused for 4 hours at 40 mU/m(2)/min (young) and 34 mU/m(2)/min (old) during both studies, and L-NMMA (0.1 mg/kg/min) was coinfused during the last 2 hours of insulin on one of these sessions. Calf blood flow was measured by venous occlusion plethysmography, and calf vascular conductance was derived from calf blood flow and mean arterial blood pressure (MABP). L-NMMA increased whole-body insulin-mediated glucose uptake (IMGU) in young subjects (from 11.22 +/- 0.08 to 12.22 +/- 0.87 mg/kg/min, P <.05) but decreased calf blood flow (from 6.53 +/- 0.62 to 5.49 +/- 0.43 mL/100 mL/min, P <.05). In contrast, L-NMMA had no effect on IMGU in elderly subjects (control v L-NMMA, 7.58 +/- 0.46 v 7.86 +/- 0.37 mg/kg/min, P = nonsignificant) but increased calf blood flow (from 3.65 +/- 0.36 to 4.50 +/- 0.32 mL/100 mL/min, P <.01). L-NMMA decreased calf vascular conductance in young subjects (from 0.083 +/- 0.008 to 0.064 +/- 0.005 mL/100 mL/min/mm Hg, P <.05) but not in the elderly (control v L-NMMA, 0.038 +/- 0.004 v 0.040 +/- 0.002 mL/100 mL/min/mm Hg), consistent with the concept that skeletal muscle endothelial NO production is reduced with age. We therefore conclude that (1) L-NMMA has different or opposite actions on calf blood flow and IMGU in both age groups, indicating that the effect of insulin on skeletal muscle blood flow is independent of its influence on glucose disposal in young and old, and (2) skeletal muscle NO production decreases with age.