INSULIN MODULATES CIRCULATING ENDOTHELIN-1 LEVELS IN HUMANS

Recent data indicate that insulin stimulates synthesis of the vasoconstrictor peptide endothelin-1 (ET-1) by cultured vascular endothelial cells in vitro. To determine whether insulin modulates ET levels in vivo and whether this effect is important in the pathogenesis of obesity-associated hypertension, we measured circulating immunoreactive ET-1 levels during euglycemic hyperinsulinemic clamps (20 mU/m2 · min-1 for 120 minutes) in eight obese women (body mass index, 36 ± 1 kg/m2) before and after 10 weeks on an 800-kcal/d protein-sparing liquid diet. During the clamp that preceded weight loss, insulin levels were increased from 17 ± 2 to 51 ± 3 mU/L and this was associated with an increment in ET-1 level from 28 ± 3 to 33 ± 3 pg/mL (P < .05). After weight loss, insulin levels were increased from 10 ± 2 to 47 ± 3 mU/L during the clamp, and there was a corresponding increase in ET-1 levels from 24 ± 3 to 30 ± 3 pg/mL (P < .025). The reduction in basal ET-1 level (from 28 ± 3 to 24 ± 3 pg/mL) with weight loss correlated strongly with the reduction in fasting immunoreactive insulin level (from 17 ± 2 to 10 ± 2 mU/L; r = .92, P < .01). The decrease in blood pressure with weight loss from 130 ± 6 73 ± 3 to 118 ± 4 72 ± 3 mm Hg) did not correlate with the corresponding reduction in circulating ET-1 levels. These results indicate that insulin modulates ET-1 levels in vivo. The importance of hyperinsulinemia-induced secretion of ET in the pathogenesis of hypertension remains to be established. © 1993.