PT - JOURNAL ARTICLE AU - Anna Rab AU - Susanne Dallinger AU - Kaija Polak AU - Johannes Pleiner AU - Elzbieta Polska AU - Michael Wolzt AU - Leopold Schmetterer TI - Specific Endothelin ET<sub>A</sub> Receptor Antagonism Does Not Modulate Insulin-Induced Hemodynamic Effects in the Human Kidney, Eye, or Forearm AID - 10.1124/jpet.103.059444 DP - 2004 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 692--696 VI - 309 IP - 2 4099 - http://jpet.aspetjournals.org/content/309/2/692.short 4100 - http://jpet.aspetjournals.org/content/309/2/692.full SO - J Pharmacol Exp Ther2004 May 01; 309 AB - There is evidence that hyperinsulinemia may stimulate endothelin-1 (ET-1) generation or release, which may affect diabetic vascular complications. BQ-123, a specific ETA receptor antagonist, was used to investigate if insulin-induced vascular effects are influenced by an acute ET-1 release. Two randomized, placebo-controlled, double-blind, cross-over studies were performed. In protocol 1, 12 healthy subjects received, on separate study days, infusions of BQ-123 (60 μg/min for 30 min) during placebo clamp conditions, BQ-123 during euglycemic hyperinsulinemia (3 mU/kg/min for 390 min), or placebo during euglycemic hyperinsulinemia. Fundus pulsation amplitude (FPA) was measured to assess pulsatile choroidal blood flow, and mean flow velocity (MFV) of the ophtalmic artery was measured by color Doppler imaging. In protocol 2, eight healthy subjects received, on separate study days, intra-arterial infusions of BQ-123 (32 μg/min for 120 min) during placebo or insulin clamp. Forearm blood flow was measured with bilateral plethysmography, expressing the ratio of responses in the intervention arm and in the control arm. Insulin alone increased FPA (+10%, p &lt; 0.001) and forearm blood flow (+19%). BQ-123 increased FPA, MFV, and forearm blood flow ratio in the absence and presence of exogenous insulin, but this effect was not different between normo- and hyperinsulinemic conditions. ET-1 plasma concentrations were not affected by insulin. In conclusion, these data do not support the concept that hyperinsulinemia increases ET-1 generation in healthy subjects. Our results, however, cannot necessarily be extrapolated to diabetic and obese subjects. The American Society for Pharmacology and Experimental Therapeutics