Hyperinsulinemia significantly reduced the pressor response to maximal norepinephrine infusion compared to saline in lean men (17.5% vs 31% increase in mean arterial pressure, p<0.001), but this mitigating effect was absent in obese men.
RCT (n=14)
Randomized crossover
No
Does euglycemic hyperinsulinemia alter the blood pressure, vascular resistance, and glucose uptake response to norepinephrine in lean versus obese men?
Insulin resistance in obesity is associated with augmented norepinephrine pressor sensitivity and decreased norepinephrine metabolic clearance, potentially contributing to obesity-related hypertension.
Absolute Event Rate: 17.5% vs 31%
p-value: p=<0.001
To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, 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 approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body (3-3Hglucose) 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 enhanced 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 approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these 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. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.
Baron et al. (1994) conducted an RCT in Obesity and Insulin Resistance (n=14). Euglycemic hyperinsulinemic clamp with norepinephrine infusion vs. Saline with norepinephrine infusion was evaluated on Percent increase in mean arterial pressure (MAP) at maximal norepinephrine dose in lean subjects (p=<0.001). Hyperinsulinemia significantly reduced the pressor response to maximal norepinephrine infusion compared to saline in lean men (17.5% vs 31% increase in mean arterial pressure, p<0.001), but this mitigating effect was absent in obese men.