N(G)-monomethyl-L-arginine alters insulin-mediated calf blood flow but notglucose disposal in the elderly

It has been proposed that an important component of glucose disposal is ins ulin-mediated vasodilation via a nitric oxide (NO)-dependent mechanism. Nor mal aging is characterized by a resistance to insulin-mediated glucose disp osal and deficient endothelial NO production. Impairment of insulin-mediate d vasodilation could contribute to this insulin resistance. We tested the h ypothesis 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 elderl y. Experiments were performed on healthy young (n = 10) and old (n = 10) su bjects 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 sessi ons. Calf blood flow was measured by venous occlusion plethysmography, and calf vascular conductance was derived from calf blood flow and mean arteria l blood pressure (MABP). L-NMMA increased whole-body insulin-mediated gluco se uptake (IMGU) in young subjects (from 11.22 +/- 0.08 to 12.22 +/- 0.87 m g/kg/min, P < .05) but decreased calf blood flow (from 6.53 +/- 0.62 to 5.4 9 +/- 0.43 mL/100 mL/min, P < .05). In contrast, L-NMMA had no effect on IM GU 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 conce pt that skeletal muscle endothelial NO production is reduced with age. We t herefore conclude that (1) L-NMMA has different or opposite actions on calf blood flow and IMGU in bath age groups, indicating that the effect of insu lin on skeletal muscle blood flow is independent of its influence on glucos e disposal in young and old, and (2) skeletal muscle NO production decrease s with age. Copyright (C) 2001 by W.B. Saunders Company.