INTERACTIONS BETWEEN INSULIN AND NOREPINEPHRINE ON BLOOD-PRESSURE ANDINSULIN SENSITIVITY - STUDIES IN LEAN AND OBESE MEN

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seve n lean (66+/-1 kg) sensitive and seven age-matched obese (96+/-3 kg) i nsulin-resistant men after an overnight fast. Both groups were normote nsive; 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 s eparate days during either saline (S) infusion or a euglycemic hyperin sulinemic clamp (I) achieving insulin concentrations of similar to 70 mu U/ml. After 180 min of either S or I, NE was infused systemically a t rates of similar to 50, 75, and 100 pg/kg per min. Glucose uptake wa s measured in whole body ([3-H-3]glucose) and in leg by the balance te chnique. 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 enhanced NE metabolic clearance by 20% in lean but no t in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a similar to 20% increase in insulin-medi ated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE presser sensiti vity and decreased NE metabolic clearance. Both of these mechanisms ca n potentially contribute to the higher incidence of hypertension in ob ese man. Insulin resistance is likely to be a predisposing but not suf ficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our r esults reflect this difference. Further studies will be required to cl arify this issue.