Effects of acute euglycemic hyperinsulinemia on urinary nitrite nitrate excretion and plasma endothelin-1 levels in men with essential hypertension and normotensive controls

Insulin stimulates the production of endothelin-1 (ET-1) and nitric oxide ( NO) by isolated endothelial cells. Additionally, insulin-dependent glucose transport and insulin-mediated NO production partially share common element s in signal transduction. There are discordant data an plasma ET-1 levels d uring acute euglycemic systemic hyperinsulinemia in normotensive men and me n with essential hypertension (EH) (known to be insulin-resistant), as well as on the relations between insulin sensitivity and vascular function. Our aim was to assess the response of approximate measures of whole-body gener ation of NO and ET-1 to acute euglycemic hyperinsulinemia in EH patients an d controls. We studied 17 newly diagnosed untreated men with uncomplicated EH and 10 normotensive controls. Plasma ET-1 and urinary excretion of nitri te plus nitrate, stable NO metabolites (Uno(x)), were measured before and d uring a 3-hour hyperinsulinemic-euglycemic clamp. Both in hypertensives and normotensives, plasma ET-1 levels were reduced after 2 hours of the clamp (EH: baseline, 3.1 +/- 1.9 pg/mL; 2 hours, 1.9 +/- 1.2 pg/mL, P =.04 v base line; controls: baseline, 4.2 +/- 2.6 pg/mL; 2 hours, 2.8 +/- 1.4 pg/mL, P =.04 v baseline). No significant changes in Uno(x) during the clamp were ob served. Changes in Uno(x) during the clamp (Delta Uno(x)) and differences i n plasma ET-1 measured before the end and before the beginning of the clamp (Delta ET-1) were correlated in the controls (r =.75, P =.01) but not in E H (r = -.01, P =.97). No parameter of glucose metabolism correlated with ba sal Uno(x) basal plasma ET-1, Delta Uno(x) and Delta ET-1, whether absolute or percent values, in either group. Thus, acute euglycemic hyperinsulinemi a produces a decrease in plasma ET-1 in both EH patients and controls. The lack of correlation between Delta Uno(x) and Delta ET-1 under these conditi ons in EH may suggest an impairment of systems governing interactions betwe en the NO-dependent pathway and ET-1. In addition, insulin actions on gluco se metabolism and on the endothelial mediators appear dissociated. Copyrigh t (C) 1999 by W.B. Saunders Company.