PHYSICAL-FITNESS AND ENDOTHELIAL FUNCTION (NITRIC-OXIDE SYNTHESIS) ARE INDEPENDENT DETERMINANTS OF INSULIN-STIMULATED BLOOD-FLOW IN NORMAL SUBJECTS

Insulin induces vasodilation via stimulation of nitric oxide (NO) synt hesis. This action of insulin exhibits considerable interindividual va riation. We determined whether the response of blood flow to endotheli um-dependent vasoactive agents correlates with that to insulin or whet her other factors, such as physical fitness, limb muscularity, or vaso dilatory capacity, better explain variations in insulin-stimulated blo od flow. Direct measurements of the forearm blood flow response to thr ee 2-h sequential doses of insulin (1, 2, and 5 mU/kg . min), endothel ium-dependent (acetylcholine and N-G-monomethyl-L-arginine) and endoth elium-independent (sodium nitroprusside) vasoactive agents, and ischem ia (reactive hyperemic forearm blood flow) were performed in 22 normal subjects (age, 24+/-1 yr; body mass index, 22.2+/-0.6 kg/m(2); maxima l aerobic power, 40+/-2 mL/kg . min). The highest insulin dose increas ed blood flow by 111+/-17%. The fraction of basal blood flow inhibited by N-G-monomethyl-L-arginine (NO synthesis-dependent flow) varied fro m 6-47%. Maximal aerobic power (r=0.52; P <0.02), the percentage of fo rearm muscle (r=0.50; P <0.02), and the NO synthesis-dependent flow (r =0.42; P <0.05), but not reactive hyperemic, acetylcholine-stimulated, or sodium nitroprusside-stimulated flow, mere significantly correlate d with insulin-stimulated (5 mU/kg . min) blood flow. In multiple line ar regression analysis, 52% of the variation (multiple R=0.72; P <0.00 1) in insulin-stimulated blood flow was explained by NO synthesis-depe ndent flow (P <0.005) and the percentage of forearm muscle (P <0.005). We conclude that endothelial function (NO synthesis-dependent basal b lood flow) and forearm muscularity are independent determinants of ins ulin-stimulated blood flow.