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 elements in signal transduction. There are discordant data on plasma ET-1 levels during acute euglycemic systemic hyperinsulinemia in normotensive men and men 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 generation of NO and ET-1 to acute euglycemic hyperinsulinemia in EH patients and controls. We studied 17 newly diagnosed untreated men with uncomplicated EH and 10 normotensive controls. Plasma ET-1 and urinary excretion of nitrite plus nitrate, stable NO metabolites (Uno(x)), were measured before and during 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 baseline; 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 observed. Changes in Uno(x) during the clamp (deltaUno(x)) and differences in plasma ET-1 measured before the end and before the beginning of the clamp (deltaET-1) were correlated in the controls (r = .75, P = .01) but not in EH (r = -.01, P = .97). No parameter of glucose metabolism correlated with basal Uno(x), basal plasma ET-1, deltaUno(x), and deltaET-1, whether absolute or percent values, in either group. Thus, acute euglycemic hyperinsulinemia produces a decrease in plasma ET-1 in both EH patients and controls. The lack of correlation between deltaUno(x) and deltaET-1 under these conditions in EH may suggest an impairment of systems governing interactions between the NO-dependent pathway and ET-1. In addition, insulin actions on glucose metabolism and on the endothelial mediators appear dissociated.
Surdacki
A
A
Institute of Cardiology, Jagiellonian University, Cracow, Poland.
Nowicki
M
M
Sandmann
J
J
Tsikas
D
D
Kruszelnicka-Kwiatkowska
O
O
Kokot
F
F
Dubiel
J S
JS
Froelich
J C
JC
D000208:Acute Disease; D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D019332:Endothelin-1 / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000652:urine*; D009573:Nitrites / Q000652:urine*; D012016:Reference Values
D001786:Blood Glucose; D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites