RELATION OF PRESSER RESPONSIVENESS TO ANGIOTENSIN-II AND INSULIN-RESISTANCE IN HYPERTENSION

To test the hypothesis that the hypertension associated with insulin r esistance is secondary to an altered responsiveness of the vasculature to presser agents, we evaluated the relationship between insulin resi stance and presser responses to angiotensin II (AII) in 21 hypertensiv e (HT) and 8 normotensive (NT) subjects on both a high (200 meg) and a low (10 meg) sodium diet. When sodium balance was achieved, each supi ne fasting subject underwent an AII infusion at a rate of 3 ng/kg per min for 60 min, with blood pressure monitored every 2 min. On the next day under similar conditions, a euglycemic hyperinsulinemic clamp was performed, with plasma glucose clamped at 90 mg/dl for 120 min. There was no significant relationship between the glucose disposal rate (M) or the insulin sensitivity index (M divided by the mean insulin level [M/I]) and blood pressure response to AII in the NTs, but a highly si gnificant (P < 0.019) negative correlation (r = -0.55) in the HTs. Fur thermore, in eight lean HTs whose body mass index was identical to tha t observed in the NTs, the relationship was even more striking (P < 0. 008; r = -0.85). The results on high and low salt diets were similar; however, the M and M/I were significantly increased (P < 0.05) in the NTs but not HTs with sodium restriction. In conclusion, HTs but not NT s display a striking correlation between presser response to AII and i nsulin resistance. This relationship is independent of the level of so dium intake. Furthermore, sodium intake modifies insulin sensitivity i n NTs but not HTs. These results strongly suggest that a primary chang e in presser response to vasoactive agents in insulin-resistant subjec ts can contribute to their elevated blood pressure.