The hypothesis relates most directly to this effect of BQ-123, and therefore the primary endpoint for analysis was the BQ-123-induced change in insulin-mediated selleck chemicals vasodilation, comparing the response between the two groups. Secondary endpoints for analysis included BQ-123-induced changes in insulin-stimulated ET-1 levels and ET-1 flux and changes in NO bioavailability, NOx levels, and NOx flux. RESULTS The subject characteristics are presented in Table 1. We studied nine lean and nine obese subjects, with full paired data available in all subjects for the primary endpoint analysis. Full data to the end of the l-NMMA stage of both paired studies were available in eight lean and six obese subjects due to technical difficulties arising during these last stages.

As expected, obese subjects had higher body mass index, waist circumference, and insulin levels. Obese subjects had marginally higher glucose and triglyceride levels, not statistically different from lean subjects. Adiponectin was significantly lower in the obese subjects. No differences across groups in the lipid profiles were seen. Table 1. Subject characteristics Matched metabolic and vascular effects of insulin. The two insulin infusion rates were chosen on the basis of their anticipated equivalence in achieving insulin-stimulated glucose disposal. This was in fact achieved (whole body glucose disposal rate of 4.9 �� 0.7 mg?kg?1?min?1 in lean vs. 5.4 �� 0.7 in obese, P = 0.59). Similarly, the steady-state arterial-venous glucose difference (lean 17.5 �� 2.5 vs. obese 20.7 �� 2.7 mg/dl, P = 0.

20) and leg glucose uptake (lean 51.2 �� 10.2 vs. obese 54.7 �� 11.0 mg/min, P = 0.31) were well matched under these conditions. As expected (28), insulin-mediated vasodilation was also well matched by this maneuver. Baseline blood flow rates were nonsignificantly higher in obese subjects (lean 0.216 �� 0.010 vs. obese 0.279 �� 0.012 l/min, P = 0.10). LVC was well matched at baseline [lean 24.4 �� 6.8 vs. obese 23.1 �� 5.8 units, P = not significant (NS)]. The increments in LVC achieved with insulin were modest (as expected given the low insulin doses used) but statistically significant, and equivalent across groups (change from baseline in LBF: lean 4.8 �� 2.7 vs. obese 5.8 �� 3.0 units; P = 0.01 for insulin, P = 0.8 comparing groups; Fig. 2, top). Steady-state blood pressure (MAP: lean 91.9 �� 4.

1 vs. obese 97.9 �� 4.4 mmHg, P = 0.23) was not statistically different across groups, suggesting Drug_discovery that the vascular and hemodynamic effects of insulin were well matched as designed. Overall, these low-dose insulin exposures induced ~22% increases in vascular conductance, and by design these changes were not statistically different across groups. Furthermore, the decrement in LVC achieved with the NOS antagonist l-NMMA was equivalent between groups (LVC reduced by 11.7 �� 4.8 units lean, by 13.9 �� 6.0 obese; P = 0.007 l-NMMA effect, P = 0.