Interactions between Insulin and Norepinephrine on Blood Pressure and Insulin Sensitivity Studies in Lean and Obese Men

To explore the interactions between insulin action and norepi-nephrine (NE) on blood pressure and muscle vascular resis-tance, we studied seven lean (66±1 kg) sensitive and seven age-matched obese (96±3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8±2.2 vs. 83.4±1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of- 70,gU/ml. After 180 min of either S or I, NE was infused systemically at rates of- 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3HJglucose) and in leg by the balance technique. The results indicate: (a) the NE /pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I en-hanced NE metabolic clearance by 20 % in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a- 20 % increase in insulin-me-diated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and de-creased NE metabolic clearance. Both ofthese mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Be-cause the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further stud-ies will be required to clarify this issue. (J. Clin. Invest. 1994